ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.487T>G (p.Tyr163Asp) (rs786203436)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166739 SCV000217550 likely pathogenic Hereditary cancer-predisposing syndrome 2019-09-20 criteria provided, single submitter clinical testing The p.Y163D variant (also known as c.487T>G), located in coding exon 4 of the TP53 gene, results from a T to G substitution at nucleotide position 487. The tyrosine at codon 163 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This alteration is located in the DNA binding domain and has been shown to be non-functional in yeast-based functional studies (<span style="background-color:initial">Kato, S et al. Proc Natl Acad Sci U S A. <span style="background-color:initial">2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). <span style="background-color:initial">Another alteration at this same location, p.Y163C, has been identified in two different Li-Fraumeni families. The proband in each case had multiple primary childhood cancers; all in the LFS spectrum of cancers. (<span style="background-color:initial">Villani et. al., Lancet Oncology<span style="background-color:initial">. 2011; 12: 559; <span style="background-color:initial">McIntyre JF, J. Clin. Oncol. 1994 May; 12(5):925-30<span style="background-color:initial">).<span style="background-color:initial"> Additionally, structural analysis had indicated that the Y163C alteration <span style="background-color:initial">results in altered fold stability and would influence both DNA binding and tetramerization (internal analysis). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD).<span style="background-color:initial"> This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. <span style="background-color:initial">Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Database of Curated Mutations (DoCM) RCV000433509 SCV000510099 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444147 SCV000510100 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426124 SCV000510101 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432709 SCV000510102 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443587 SCV000510103 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425235 SCV000510104 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435516 SCV000510105 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417885 SCV000510106 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424608 SCV000510107 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434903 SCV000510108 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420721 SCV000510109 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430982 SCV000510110 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441262 SCV000510111 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420162 SCV000510112 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only

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