Variant Annotation
Available parameters and response documentation is available here
GET /lookup/chr17:7578443:A:T?add-AMP-annotation=1&format=api
{ "chromosome": "chr17", "alt": "T", "ref": "A", "pos": 7578443, "variant_id": "10190170075784430004", "regions": { "uniprot_regions": { "version": "07-Nov-2025", "items": [ { "absolute_positon": 1076661175, "amino_acid": "M1-L25,L25-L32,S33-T125,Y126-G187,G187-E224,V225-S261,S261-A307,A307-Q331,I332-S367,S367-D393", "chromo": "chr17", "colour": "255,0,0", "description": null, "length": 9027, "position": 7571731, "protein": "P53_HUMAN", "type": "homo_sapiens proteome sequences", "pub_med_references": null }, { "absolute_positon": 1076661175, "amino_acid": "M1-L25,L25-L32,S33-T125,Y126-G187,G187-E224,V225-S261,S261-A307,A307-Q331,I332-S367,S367-D393", "chromo": "chr17", "colour": "255,0,0", "description": null, "length": 9166, "position": 7571731, "protein": "P53_HUMAN", "type": "homo_sapiens proteome sequences", "pub_med_references": null }, { "absolute_positon": 1076661183, "amino_acid": "M1-L25,L25-L32,S33-T125,Y126-G187,G187-E224,V225-S261,S261-A307,A307-Q331,I332-S367,S367-D393", 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"position": 7577038, "protein": "P53_HUMAN", "type": "region of interest", "pub_med_references": null }, { "absolute_positon": 1076666506, "amino_acid": "S116-K292", "chromo": "chr17", "colour": "255,102,0", "description": "Interaction with AXIN1", "length": 2280, "position": 7577062, "protein": "P53_HUMAN", "type": "region of interest", "pub_med_references": null }, { "absolute_positon": 1076666506, "amino_acid": "T102-K292", "chromo": "chr17", "colour": "0,153,51", "description": "DNA-binding region_102-292", "length": 2322, "position": 7577062, "protein": "P53_HUMAN", "type": "DNA-binding domain", "pub_med_references": null }, { "absolute_positon": 1076667017, "amino_acid": "F113-Y236", "chromo": "chr17", "colour": "255,102,0", "description": "Required for interaction with FBXO42", "length": 1778, "position": 7577573, "protein": "P53_HUMAN", "type": "region of interest", "pub_med_references": null } ] }, "nih_gtex": { "version": "v10", "items": [ { "GTExJsonData": { "exon_id": 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The tyrosine at codon 163 is replaced by asparagine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic." ], "review_description": "Likely pathogenic", "submitter_name": "Ambry Genetics", "review_date": 20250514, "origin": "germline", "diseases": [ { "symbols": { "medgen": "C0027672" } } ], "method": "clinical testing", "date_updated": 20250713, "clinical_significance": [ "Likely pathogenic" ], "review_status": "criteria provided, single submitter", "accession_id": "SCV002638731" } ], "submission_description": [], "review_date": 20250514, "diseases": [ { "pub_med": [ 25394175 ], "symbols": { "medgen": "C0027672", "mesh": "D009386", "mondo": "MONDO:0015356" }, "normalized_disease": [ "Hereditary Neoplastic Syndrome" ], "names": [ "Hereditary Cancer-Predisposing Syndrome", "Hereditary Neoplastic Syndrome", "Tumor Predisposition", "Hereditary Neoplastic Syndrome", "Hereditary Neoplastic Syndrome" ], "normalized_cancer": [ "Tumor predisposition", "Hereditary Cancer Syndrome" ], "keyword": "Hereditary cancer syndrome" } ], "title": "NM_000546.6(TP53):c.487T>A (p.Tyr163Asn) AND Hereditary cancer-predisposing syndrome", "date_created": 20221129, "clinical_significance": [ "Likely pathogenic" ], "variant_id": 10190170075784430004, "review_description": "Likely pathogenic", "allele_id": 363558, "accession_id": "RCV002338982" }, { "variation_id": 376679, "submissions": [ { "submitter_date": 20240422, "submission_description": [ "This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 10229196, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]." ], "review_description": "Likely pathogenic", "submitter_name": "Myriad Genetics, Inc.", "review_date": 20240214, "origin": "unknown", "diseases": [ { "symbols": { "omim": "151623" } } ], "method": "clinical testing", "date_updated": 20240501, "clinical_significance": [ "Likely pathogenic" ], "review_status": "criteria provided, single submitter", "accession_id": "SCV004932800" } ], "submission_description": [], "review_date": 20240214, "diseases": [ { "pub_med": [ 17392385, 20065170, 12692171, 15604628, 23788249, 24493721, 25394175, 25356965, 26389258, 26324357 ], "symbols": { "orphanet": "524", "omim": "151623", "medgen": "C1835398", "gene": "553989" }, "normalized_disease": [ "Li-Fraumeni Syndrome" ], "names": [ "Li-Fraumeni Syndrome" ] } ], "title": "NM_000546.6(TP53):c.487T>A (p.Tyr163Asn) AND Li-Fraumeni syndrome 1", "date_created": 20240501, "clinical_significance": [ "Likely pathogenic" ], "variant_id": 10190170075784430004, "review_description": "Likely pathogenic", "allele_id": 363558, "accession_id": "RCV004022250" }, { "variation_id": 376679, "submissions": [ { "submitter_date": 20250207, "submission_description": [ "This sequence change replaces tyrosine with asparagine at codon 163 of the TP53 protein (p.Tyr163Asn). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376679). Experimental studies in yeast have shown that this missense change disrupts TP53 transactivation activity (PMID:¬†12826609). A different missense substitution at this codon (p.Tyr163Cys) has been determined to be pathogenic (Invitae). This suggests that the tyrosine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance." ], "review_description": "Uncertain significance", "submitter_name": "Labcorp Genetics (formerly Invitae), Labcorp", "review_date": 20170824, "origin": "germline", "diseases": [ { "symbols": { "medgen": "C0085390" } } ], "method": "clinical testing", "date_updated": 20250225, "clinical_significance": [ "Uncertain significance" ], "review_status": "criteria provided, single submitter", "accession_id": "SCV000754569" } ], "submission_description": [], "review_date": 20170824, "diseases": [ { "pub_med": [ 17392385, 24493721, 26389210, 26389258 ], "normalized_cancer": [ "Sarcoma family syndrome of Li and Fraumeni" ], "symbols": { "omim": "151623", "medgen": "C0085390", "mondo": "MONDO:0018875" }, "normalized_disease": [ "Li-Fraumeni Syndrome" ], "names": [ "Li-Fraumeni Syndrome", "Sarcoma Family Syndrome Li Fraumeni" ] } ], "title": "NM_000546.6(TP53):c.487T>A (p.Tyr163Asn) AND Li-Fraumeni syndrome", "date_created": 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[ "CGD" ], "pub_med_id": 6016796 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 3480372 }, { "referenced_by": [ "CGD" ], "pub_med_id": 3409256 }, { "referenced_by": [ "gene2phenotype", "GenCC" ], "pub_med_id": 2259385 }, { "referenced_by": [ "gene2phenotype", "GenCC", "CGD" ], "pub_med_id": 1978757 }, { "referenced_by": [ "gene2phenotype", "GenCC" ], "pub_med_id": 1933902 }, { "referenced_by": [ "gene2phenotype", "GenCC" ], "pub_med_id": 1683921 }, { "referenced_by": [ "gene2phenotype", "GenCC", "CGD" ], "pub_med_id": 1679237 }, { "referenced_by": [ "gene2phenotype", "GenCC" ], "pub_med_id": 1644930 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 1642235 }, { "referenced_by": [ "CGD" ], "pub_med_id": 1591732 }, { "referenced_by": [ "gene2phenotype", "GenCC", "CGD" ], "pub_med_id": 1565144 }, { "referenced_by": [ "gene2phenotype", "GenCC", "CGD" ], "pub_med_id": 1565143 }, { "referenced_by": [ "CGD" ], "pub_med_id": 1349175 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 191170 } ], "gene_symbol": "TP53", "gene_id": 33956 } ] }, "publication_counts": [ { "type": "variant", "id": "10190170075784430004", "count": 23 }, { "type": "gene", "id": 33956, "count": 55314, "symbol": "TP53" } ], "uniprot_variants": [ { "version": "07-Jul-2025", "items": [ { "annotation_id": "VAR_044871", "protein_id": "E7EQX7", "proteinname": "Cellular tumor antigen p53", "somaticstatus": "False", "frequency": null, "gene": "TP53", "clinicalsignificances": [ "Likely pathogenic", "Unclassified" ], "transcripts": [ "ENST00000413465" ], "association": [ { "disease": "Cystic, Mucinous and Serous Neoplasms", "disease_description": "From tissue: Ovary", "disease_symbol": null, "disease_alt_symbol": null, "evidences": null }, { "disease": "Gliomas", "disease_description": "From tissue: Cerebrum", "disease_symbol": null, "disease_alt_symbol": null, "evidences": null }, { "disease": "Hereditary cancer-predisposing syndrome", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Li-Fraumeni syndrome ", "disease_description": "Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a broad spectrum of cancers including early-onset cancers.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Li-Fraumeni syndrome 1 ", "disease_description": "Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a broad spectrum of cancers including early-onset cancers.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Nerve Sheath Tumors", "disease_description": "From tissue: Retroperitoneum", "disease_symbol": null, "disease_alt_symbol": null, "evidences": null }, { "disease": "Squamous Cell Neoplasms", "disease_description": "From tissue: Head, face or neck, NOS", "disease_symbol": null, "disease_alt_symbol": null, "evidences": null } ], "siftscore": null, "siftprediction": null, "polyphenscore": null, "polyphenprediction": null, "evidences": null, "xrefs": { "cosmicmutationid": [ "COSV52676168" ], "clinvaraccession": [] }, "variant_type": "Unclassified", "disease": "Cystic, Mucinous and Serous Neoplasms", "disease_symbol": null, "disease_alt_symbol": null, "bed_comments": null, "pub_med_references": null } ] } ], "wustl_civic": [ { "version": "07-Oct-2025", "items": [ { "asco_entry": null, "clinical_significance": "Dominant Negative", "disease": null, "doid": null, "drug_interaction_type": null, "drugs": null, "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/10272", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "A set of previously characterized p53 mutants was tested in the yeast assay to understand their transdominant potential (dominant negative). Each mutant was expressed equally with the wild-type p53. The authors used the p21, bax, and PIG3 sequences as p53 binding sites. TP53 variant Y163N was classified as recessive for p21, but it was classified as dominant negative for bax and PIG3. In addition, Y163N was classified as a hotspot for mutation (P < 0.001) by the authors. The authors proposed a hierarchy of dominance of p53 variants for p21, PIG3, and bax sequences. They observed p53 variants that are dominant negative for p21 are also dominant for PIG3 and bax, and p53 variants that are dominant negative for PIG3 are also dominant for bax. The authors suggested lack of transactivation ability is necessary but not sufficient to predict dominance.", "evidence_status": "accepted", "evidence_type": "Functional", "gene": "TP53", "gene_civic_url": null, "last_review_date": "2023-01-09 21:47:12 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 11896595 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "Y163N", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/3668", "molecular_profiles": null } ] } ], "nih_gdc": [ { "version": "07-Jun-2025", "sex": [ { "key": "Female", "value": 3 } ], "age_freq": [ { "key": "30-40", "value": 2 }, { "key": "50-60", "value": 1 } ], "os_status": [ { "key": "Living", "value": 2 }, { "key": "Deceased", "value": 1 } ], "race": [ { "key": "White", "value": 2 } ], "tumor_status": [ { "key": "Recurred", "value": 2 } ], "tumor_tissue_site": null, "path_t_stage": null, "path_n_stage": null, "path_m_stage": null, "clin_t_stage": null, "clin_n_stage": null, "clin_m_stage": null, "ajcc_pathologic_tumor_stage": null, "total_samples": 3, "study_name": null, "prior_dx": [ { "key": "No", "value": 2 } ], "drug": null, "measure_of_response": null, "therapy_type": [ { "key": "Chemotherapy", "value": 7 } ], "route_of_administration": [ { "key": "Iv", "value": 5 }, { "key": "Ip", "value": 1 } ], "therapy_ongoing": [ { "key": "NO", "value": 6 }, { "key": "YES", "value": 1 } ], "clinical_significance": [ { "key": "Likely Pathogenic", "value": 3 }, { "key": "Uncertain Significance", "value": 3 } ], "pub_med_references": null, "oncotree_code": [ { "key": "ASTR", "value": 1 }, { "key": "OVARY", "value": 1 } ], "cancer_name": [ { "key": "Astrocytoma", "value": 1 }, { "key": "Malignant Peripheral Nerve Sheath Tumors (MPNST)", "value": 1 }, { "key": "Serous Cystadenocarcinoma", "value": 1 } ], "cancer_type": [ { "key": "Glioma", "value": 1 }, { "key": "Malignant Peripheral Nerve Sheath Tumors (MPNST)", "value": 1 }, { "key": "Ovarian/Fallopian Tube Cancer", "value": 1 } ], "tissue_type": [ { "key": "CNS/Brain", "value": 1 }, { "key": "Malignant Peripheral Nerve Sheath Tumors (MPNST)", "value": 1 }, { "key": "Ovary/Fallopian Tube", "value": 1 } ] } ], "saphetor_known_pathogenicity": [ { "version": "21-Oct-2025", "items": [ { "annotations": { "NCBI ClinVar2": [ { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "NCBI ClinVar2", "codon": 163, "gene_symbol": "TP53", "hgvs": "Y163N", "transcript": "NM_000546.6", "submission_count": 3, "review_stars": 1, "accession_count": 3, "publication_count": 1, "clinical_significance": [ "conflicting interpretations of pathogenicity" ], "pub_med_references": [ 10229196 ], "disease_name": [ "Hereditary Cancer-Predisposing Syndrome", "Hereditary Neoplastic Syndrome", "Li-Fraumeni Syndrome", "Sarcoma Family Syndrome Li Fraumeni", "Tumor Predisposition" ], "is_conflicting": true, "submissions_b": 0, "submissions_p": 2, "submissions_vus": 1 } ], "UNIPROT UniProt Variants": [ { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "UNIPROT UniProt Variants", "codon": 163, "gene_symbol": "TP53", "hgvs": "Y163N", "transcript": "NM_000546.6", "disease_name": [ "Cystic, Mucinous and Serous Neoplasms", "Gliomas", "Hereditary cancer-predisposing syndrome", "Li-Fraumeni syndrome", "Li-Fraumeni syndrome 1" ], "annotation_id": "VAR_044871" } ] } } ] } ], "alpha_missense": [ { "version": "03-Jul-2024", "main_data": "Likely Pathogenic", "alpha_missense_score": 0.9957884456923124 } ], "acmg_annotation": { "version_name": "13.12.3", "gene_symbol": "TP53", "transcript": "NM_000546.6", "transcript_reason": "MANE select", "coding_impact": "missense", "blosum_score": -5, "verdict": { "ACMG_rules": { "benign_score": 0, "benign_subscore": "Uncertain Significance", "clinical_score": 4.256, "pathogenic_score": 6, "pathogenic_subscore": "Likely Pathogenic", "total_score": 6, "verdict": "Likely Pathogenic" }, "classifications": [ "PM1", "PM5", "PM2_Supporting", "PP5" ] }, "classifications": [ { "name": "PM1", "met_criteria": true, "user_explain": [ "Hot-spot of length 17 amino-acids has 103 missense/in-frame variants (31 pathogenic variants, 71 uncertain variants, and 1 benign variant), which qualifies as strong pathogenic.", "UniProt protein P53_HUMAN region of interest 'Required for interaction with FBXO42' has 666 missense/in-frame variants (214 pathogenic variants, 440 uncertain variants, and 12 benign variants), which qualifies as moderate pathogenic.", "UniProt protein P53_HUMAN DNA-binding domain 'DNA-binding region_102-292' has 1 114 missense/in-frame variants (399 pathogenic variants, 700 uncertain variants, and 15 benign variants), which qualifies as moderate pathogenic.", "UniProt protein P53_HUMAN region of interest 'Interaction with AXIN1' has 1 038 missense/in-frame variants (371 pathogenic variants, 653 uncertain variants, and 14 benign variants), which qualifies as moderate pathogenic.", "UniProt protein P53_HUMAN region of interest 'Required for interaction with ZNF385A' has 1 147 missense/in-frame variants (400 pathogenic variants, 732 uncertain variants, and 15 benign variants), which qualifies as moderate pathogenic.", "UniProt protein P53_HUMAN region of interest 'Interaction with CCAR2' has 1 505 missense/in-frame variants (406 pathogenic variants, 1 041 uncertain variants, and 58 benign variants), which qualifies as supporting pathogenic.", "UniProt protein P53_HUMAN region of interest 'Interaction with HIPK1' has 1 416 missense/in-frame variants (422 pathogenic variants, 936 uncertain variants, and 58 benign variants), which qualifies as supporting pathogenic.", "Limiting strength to Moderate due to co-occurrence with other predictive evidence." ] }, { "name": "PM5", "met_criteria": true, "user_explain": [ "Alternative variant ##chr17:7578442 T⇒C## (Tyr163Cys) is classified Pathogenic, 3 stars, by ClinVar (confirmed using the germline classifier)." ] }, { "name": "PM2", "met_criteria": true, "user_explain": [ "Variant not found in gnomAD genomes, good gnomAD genomes coverage = 31.9.", "Variant not found in gnomAD exomes, good gnomAD exomes coverage = 88.3." ], "strength": "Supporting" }, { "name": "PP5", "met_criteria": true, "user_explain": [ "Supporting: ClinVar classifies this variant as Uncertain Significance but a high confidence submitter has classified as Likely Pathogenic, 1 star (reviewed May '25, 3 submissions of which 1 is from high confidence submitter), citing %%PUBMED:10229196%%." ] } ], "gene_id": 33956, "sample_findings": { "phenotypes": "No matching phenotype found for gene TP53 which is associated with Adrenocortical Carcinoma, Hereditary, Adult Hepatocellular Carcinoma, Alveolar Rhabdomyosarcoma, B-Cell Chronic Lymphocytic Leukemia, and 25 more, according to CGD, ClinGen Disease Validity, GenCC, Mondo, and gene2phenotype.", "mode_of_inheritance": "AD, based on gene information from CGD, ClinGen Disease Validity, GenCC, Mondo, and gene2phenotype." } }, "amp_annotation": { "version_name": "13.12.3", "verdict": { "tier": "Tier I", "approx_score": 3.3249999999999997 }, "classifications": [ { "name": "Crtd", "tier": "Tier I", "user_explain": { "Tier I": [ "AML with Myelodysplasia-Related Changes, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Essential Thrombocythemia, and 5 more, prognostic, curated, from OncoKB, citing %%PUBMED:29296692%%, %%PUBMED:28819011%%, %%PUBMED:26022239%%, %%PUBMED:25952993%%, and 20 more. No patient information was provided to match the cancer." ], "Tier III": [ "Variant not found in CKB." ] }, "approx_score": 9.0 }, { "name": "Drug", "tier": "Tier II", "user_explain": { "Tier II": [ "12 therapies (Azacitidine, Capecitabine + Cetuximab + Oxaliplatin, Carboplatin + Cisplatin, Cisplatin, and 8 more), Actionable, curated, from CIViC. Related to Esophagus/Stomach, Breast Cancer, Lung Cancer, Solid Tumor, and 3 more. No patient information was provided to match the cancer." ], "Tier III": [ "6 therapies (Alemtuzumab, Cisplatin, Doxorubicin, Etoposide, and 2 more), Actionable, curated, from CIViC. Related to Esophagus/Stomach, Breast Cancer, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, and Sarcoma, NOS. No patient information was provided to match the cancer.", "No additional relevant drugs or clinical trials found in AACT, CIViC genes, CKB Genes, DGI, or PharmGKB." ] }, "approx_score": 8.0 }, { "name": "Germ", "tier": "Tier II", "user_explain": { "Tier II": [ "This missense variant is classified Likely Pathogenic by the germline classifier, using rules PM1, PM5, PM2_Supporting, and PP5." ] }, "approx_score": 7.0 }, { "name": "Path", "tier": "Tier I", "user_explain": { "Tier I": [ "The Human Protein Atlas classifies TP53 as tumour-suppressing." ], "Tier II": [ "GHR reports that the TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). Also, associates TP53 with the following 9 cancers: Bladder/Urinary Tract, Breast, Cholangiocarcinoma, Head and Neck Squamous Cell Carcinoma, Li-Fraumeni Syndrome, and 4 more.", "Mondo associates gene TP53 with the following 26 cancers: Adrenocortical Carcinoma, Hereditary, Adult Hepatocellular Carcinoma, Alveolar Rhabdomyosarcoma, B-Cell Chronic Lymphocytic Leukemia, B-Lymphoblastic Leukemia/Lymphoma T(9;22)(Q34.1;Q11.2), and 21 more." ] }, "approx_score": 6.0 }, { "name": "Pubs", "tier": "Tier III", "user_explain": { "Tier III": [ "No publications have been linked by VarSome users." ] }, "approx_score": 5.0 }, { "name": "Soma", "tier": "Tier I", "user_explain": { "Tier I": [ "This variant is reported in 68 out of the 42 872 somatic samples for gene TP53, which has 5 872 reported somatic variants. It is not found in GnomAD. This is statistically rated Tier I." ], "Tier III": [ "TP53 Somatic reports 25 samples, cancer_type = 8 x Breast Cancer, NOS, 4 x Cancer of Unknown Primary, 3 x Hepatobiliary Cancer, and 9 more, tissue_type = 8 x Breast, 4 x Other, 2 x Liver, and 11 more.", "CBioPortal reports 31 samples, cancer type = 6 x Hepatobiliary Cancer, 6 x Prostate Cancer, 4 x Non-Small Cell Lung Cancer, and 8 more, sample type = 17 x Primary, 7 x Metastasis, and 1 x Metastatic, tissue = 6 x Liver, 6 x Prostate, 4 x Lung, and 8 more.", "CancerHotspots reports 9 samples, bio-type = 1 x protein_coding, cancer type = 3 x Hepatobiliary Cancer, 1 x Esophagogastric Cancer, 1 x Glioma, and 3 more, tissue site = 3 x Liver, 1 x CNS/Brain, 1 x Esophagus/Stomach, and 3 more.", "GDC reports 3 samples, drugs = 2 x Carboplatin, 2 x Taxol, 1 x Cisplatin, and 2 more, outcomes = 2 x Recurred, sex = 3 x Female, tissues = 1 x CNS/Brain, 1 x Malignant Peripheral Nerve Sheath Tumors (MPNST), and 1 x Ovary/Fallopian Tube.", "Variant not found in ICGC or TP53 Germline." ] }, "total_samples": 68, "approx_score": 4.0 }, { "name": "Freq", "tier": "Tier II", "user_explain": { "Tier II": [ "Variant not found in gnomAD genomes, good gnomAD genomes coverage = 31.9.\nVariant not found in gnomAD exomes, good gnomAD exomes coverage = 88.3." ] }, "approx_score": 3.0 }, { "name": "Type", "tier": "Tier III", "user_explain": { "Tier III": [ "No relevant information.", "Variant is not predicted splicing: no prediction from MaxEntScan." ] }, "approx_score": 2.0 }, { "name": "Pred", "tier": "Tier III", "user_explain": { "Tier III": [ "No relevant information." ] }, "approx_score": 1.0 } ] }, "cbio_portal": [ { "version": "06-Jun-2023", "total_samples": 31, "sample_id": null, "sample_type": [ { "key": "Primary", "value": 17 }, { "key": "Metastasis", "value": 7 }, { "key": "Metastatic", "value": 1 } ], "study_name": null, "mutation_status": [ { "key": "Somatic", "value": 16 } ], "validation_status": [ { "key": "Valid", "value": 4 } ], "center": [ { "key": "Mskcc", "value": 11 }, { "key": "Broad.Mit.Edu", "value": 2 }, { "key": "Fhcrc", "value": 2 }, { "key": "Genome.Wustl.Edu", "value": 2 }, { "key": "Bgi", "value": 1 }, { "key": "Inserm.Fr", "value": 1 }, { "key": "Mdanderson.Org/Ucsc.Edu/Broad.Mit.Edu", "value": 1 }, { "key": "Msk-Impact410", "value": 1 }, { "key": "Riken", "value": 1 } ], "t_ref_count": 4404, "t_alt_count": 3928, "n_ref_count": 6881, "n_alt_count": 2, "n_depth": 415, "t_depth": 318, "canonical": true, "hotspot": false, "ensp": "ENSP00000269305", "ccds": "CCDS11118.1", "cdsposition": "487", "cdnaposition": "677", "biotype": "Protein_Coding", "uniparc": "UPI000002ED67", "pick": 1.0, "sex": [ { "key": "Male", "value": 18 }, { "key": "Female", "value": 11 } ], "age_freq": [ { "key": "50-60", "value": 6 }, { "key": "30-40", "value": 5 }, { "key": "70-80", "value": 3 } ], "os_months": [ { "key": "11", "value": 3 }, { "key": "13", "value": 3 }, { "key": "7", "value": 2 }, { "key": "77", "value": 2 }, { "key": "15", "value": 1 }, { "key": "16", "value": 1 }, { "key": "2", "value": 1 }, { "key": "3", "value": 1 }, { "key": "33", "value": 1 }, { "key": "35", "value": 1 }, { "key": "47", "value": 1 }, { "key": "9", "value": 1 } ], "os_status": [ { "key": "Living", "value": 13 }, { "key": "Deceased", "value": 8 } ], "race": [ { "key": "European (non-Finnish)", "value": 10 } ], "tumor_status": [ { "key": "Recurred", "value": 4 } ], "dfs_months": [ { "key": "55", "value": 2 }, { "key": "10", "value": 1 }, { "key": "7", "value": 1 } ], "path_t_stage": null, "pfs_status": [ { "key": "Yes", "value": 3 }, { "key": "No", "value": 1 } ], "radiation_therapy": [ { "key": "Yes", "value": 2 }, { "key": "No", "value": 1 } ], "path_n_stage": null, "path_m_stage": null, "new_tumor_event_after_initial_treatment": [ { "key": "No", "value": 1 }, { "key": "YES", "value": 1 }, { "key": "Yes", "value": 1 } ], "ajcc_pathologic_tumor_stage": null, "dss_status": [ { "key": "0:Alive Or Dead Tumor Free", "value": 2 }, { "key": "1.0", "value": 1 }, { "key": "1:Dead With Tumor", "value": 1 } ], "prior_dx": [ { "key": "No", "value": 2 } ], "somatic_status_freq": [ { "key": "Yes", "value": 23 } ], "grade": [ { "key": "G2", "value": 3 }, { "key": "G3", "value": 2 } ], "pub_med_references": null, "oncotree_code": [ { "key": "HCC", "value": 6 }, { "key": "PRAD", "value": 6 }, { "key": "LUAD", "value": 4 }, { "key": "MPNST", "value": 3 }, { "key": "DIFG", "value": 2 }, { "key": "SOC", "value": 2 }, { "key": "CHL", "value": 1 }, { "key": "ESCA", "value": 1 }, { "key": "ESCC", "value": 1 }, { "key": "GBM", "value": 1 }, { "key": "HGSOC", "value": 1 }, { "key": "MEL", "value": 1 }, { "key": "PANCREAS", "value": 1 }, { "key": "USC", "value": 1 } ], "cancer_name": [ { "key": "Hepatobiliary Cancer", "value": 6 }, { "key": "Prostate Cancer", "value": 6 }, { "key": "Non-Small Cell Lung Cancer", "value": 4 }, { "key": "Glioma", "value": 3 }, { "key": "Esophagogastric Cancer", "value": 2 }, { "key": "Nerve Sheath Tumor", "value": 2 }, { "key": "Ovarian Cancer", "value": 2 }, { "key": "Endometrial Cancer", "value": 1 }, { "key": "Hodgkin Lymphoma", "value": 1 }, { "key": "Melanoma", "value": 1 }, { "key": "Ovarian Epithelial Tumor", "value": 1 }, { "key": "Pancreatic Cancer", "value": 1 }, { "key": "Sarcoma", "value": 1 } ], "cancer_type": [ { "key": "Hepatobiliary Cancer", "value": 6 }, { "key": "Prostate Cancer", "value": 6 }, { "key": "Non-Small Cell Lung Cancer", "value": 4 }, { "key": "Glioma", "value": 3 }, { "key": "Nerve Sheath Tumor", "value": 3 }, { "key": "Ovarian Cancer", "value": 3 }, { "key": "Esophagogastric Cancer", "value": 2 }, { "key": "Endometrial Cancer", "value": 1 }, { "key": "Hodgkin Lymphoma", "value": 1 }, { "key": "Melanoma", "value": 1 }, { "key": "Pancreatic Cancer, NOS", "value": 1 } ], "tissue_type": [ { "key": "Liver", "value": 6 }, { "key": "Prostate", "value": 6 }, { "key": "Lung", "value": 4 }, { "key": "CNS/Brain", "value": 3 }, { "key": "Ovary/Fallopian Tube", "value": 3 }, { "key": "Peripheral Nervous System", "value": 3 }, { "key": "Esophagus/Stomach", "value": 2 }, { "key": "Lymphoid", "value": 1 }, { "key": "Pancreas", "value": 1 }, { "key": "Skin", "value": 1 }, { "key": "Uterus", "value": 1 } ] } ], "cancer_hotspots": [ { "version": "10-Sep-2021", "total_samples": 9, "t_ref_count": 381, "t_alt_count": 374, "n_ref_count": null, "n_alt_count": null, "n_depth": 0, "t_depth": 1678, "somatic": null, "canonical": true, "ensp": "ENSP00000269305", "ccds": "CCDS11118.1", "cdsposition": "487/1182", "cdnaposition": "677/2579", "biotype": "protein_coding", "feature": "ENST00000269305", "uniparc": "Upi000002Ed67", "pick": 1.0, "pub_med_references": null, "oncotree_code": [ { "key": "HCC", "value": 3 }, { "key": "CHL", "value": 1 }, { "key": "ESCA", "value": 1 }, { "key": "LGGNOS", "value": 1 }, { "key": "LUAD", "value": 1 }, { "key": "SOC", "value": 1 } ], "cancer_name": [ { "key": "Hepatocellular Carcinoma", "value": 3 }, { "key": "Classical Hodgkin Lymphoma", "value": 1 }, { "key": "Esophageal Adenocarcinoma", "value": 1 }, { "key": "Low-Grade Glioma, NOS", "value": 1 }, { "key": "Lung Adenocarcinoma", "value": 1 }, { "key": "Serous Ovarian Cancer", "value": 1 } ], "cancer_type": [ { "key": "Hepatobiliary Cancer", "value": 3 }, { "key": "Esophagogastric Cancer", "value": 1 }, { "key": "Glioma", "value": 1 }, { "key": "Hodgkin Lymphoma", "value": 1 }, { "key": "Non-Small Cell Lung Cancer", "value": 1 }, { "key": "Ovarian Cancer", "value": 1 } ], "tissue_type": [ { "key": "Liver", "value": 3 }, { "key": "CNS/Brain", "value": 1 }, { "key": "Esophagus/Stomach", "value": 1 }, { "key": "Lung", "value": 1 }, { "key": "Lymphoid", "value": 1 }, { "key": "Ovary/Fallopian Tube", "value": 1 } ] } ], "phylop100way": [ { "version": "13-Apr-2021", "conservation_score": [ "9.291" ] } ], "maxentscan": null, "oncokb": [ { "version": "v5.3", "allele_exist": true, "diagnostic_implications": null, "diagnostic_summary": "", "gene_exist": true, "gene_summary": "TP53, a tumor suppressor in the DNA damage pathway, is the most frequently mutated gene in cancer.", "highest_diagnostic_implication_level": null, "highest_fda_level": null, "highest_prognostic_implication_level": "LEVEL_Px1", "highest_resistance_level": null, "highest_sensitive_level": null, "hotspot": true, "last_update": "05/18/2017", "mutation_effect": { "citations": { "abstracts": [], "pmids": [ "10229196" ] }, "description": "The TP53 Y163N mutation occurs in the protein's DNA binding domain. Expression of this mutation in osteosarcoma cell lines that lack wildtype TP53 is associated with decreased transcriptional activation of the p53 target gene p21. Additionally, cell lines expressing this mutation have decreased apoptosis and enhanced cell growth as compared to cell lines that express wildtype form of TP53 (PMID: 10229196) suggesting that this mutation confers loss of p53 function.", "knowneffect": "Likely Loss-of-function" }, "oncogenic": "Likely Oncogenic", "other_significant_resistance_levels": null, "other_significant_sensitive_levels": null, "prognostic_implications": [ { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "25412851", "25860933" ], "tumor_type": { "children": {}, "code": "AMLMRC", "color": "LightSalmon", "id": 612, "level": 4, "main_type": { "id": null, "name": "Leukemia", "tumor_form": "LIQUID" }, "name": "AML with Myelodysplasia-Related Changes", "parent": "AML", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "22186996", "18596741" ], "tumor_type": { "children": {}, "code": "AML", "color": "LightSalmon", "id": 476, "level": 3, "main_type": { "id": null, "name": "Leukemia", "tumor_form": "LIQUID" }, "name": "Acute Myeloid Leukemia", "parent": "MNM", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "25412846", "25952993" ], "tumor_type": { "children": {}, "code": "TMN", "color": "LightSalmon", "id": 663, "level": 4, "main_type": { "id": null, "name": "Leukemia", "tumor_form": "LIQUID" }, "name": "Therapy-Related Myeloid Neoplasms", "parent": "AML", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "23243274", "24004666", "20697090", "19188171", "24652989" ], "tumor_type": { "children": {}, "code": "CLLSLL", "color": "LimeGreen", "id": 806, "level": 5, "main_type": { "id": null, "name": "Mature B-Cell Neoplasms", "tumor_form": "LIQUID" }, "name": "Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma", "parent": "MBN", "tissue": "Lymphoid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "21714648", "25092778", "24220272" ], "tumor_type": { "children": {}, "code": "MDS", "color": "LightSalmon", "id": 411, "level": 3, "main_type": { "id": null, "name": "Myelodysplastic Syndromes", "tumor_form": "LIQUID" }, "name": "Myelodysplastic Syndromes", "parent": "MNM", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "24478400", "29296692", "22887079" ], "tumor_type": { "children": {}, "code": "ET", "color": "LightSalmon", "id": 709, "level": 4, "main_type": { "id": null, "name": "Myeloproliferative Neoplasms", "tumor_form": "LIQUID" }, "name": "Essential Thrombocythemia", "parent": "MPN", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "25516983", "22052707", "22887079" ], "tumor_type": { "children": {}, "code": "MPN", "color": "LightSalmon", "id": 343, "level": 3, "main_type": { "id": null, "name": "Myeloproliferative Neoplasms", "tumor_form": "LIQUID" }, "name": "Myeloproliferative Neoplasms", "parent": "MNM", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px1", "pmids": [ "25516983", "22052707", "22887079" ], "tumor_type": { "children": {}, "code": "PMF", "color": "LightSalmon", "id": 699, "level": 4, "main_type": { "id": null, "name": "Myeloproliferative Neoplasms", "tumor_form": "LIQUID" }, "name": "Primary Myelofibrosis", "parent": "MPN", "tissue": "Myeloid", "tumor_form": "LIQUID" } }, { "abstracts": [], "alterations": [ "Oncogenic Mutations" ], "description": "", "level_of_evidence": "LEVEL_Px3", "pmids": [ "8639789", "7579380", "28819011", "24684350", "26022239" ], "tumor_type": { "children": {}, "code": "MCL", "color": "LimeGreen", "id": 810, "level": 5, "main_type": { "id": null, "name": "Mature B-Cell Neoplasms", "tumor_form": "LIQUID" }, "name": "Mantle Cell Lymphoma", "parent": "MBN", "tissue": "Lymphoid", "tumor_form": "LIQUID" } } ], "prognostic_summary": "", "query": { "canonicaltranscript": null, "proteinstart": null, "id": null, "referencegenome": "GRCh37", "hugosymbol": "TP53", "hgvsinfo": null, "entrezgeneid": 7157, "alterationtype": null, "svtype": null, "alteration": "Y163N", "tumortype": null, "hgvs": null, "consequence": null, "proteinend": null }, "treatments": null, "tumor_type_summary": "", "variant_exist": true, "variant_summary": "The TP53 Y163N mutation is likely oncogenic.", "variant_id": null, "vus": false } ] }