ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.476C>A (p.Ala159Asp)

dbSNP: rs1555526131
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001326770 SCV001517819 pathogenic Li-Fraumeni syndrome 2022-04-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala159 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in individuals with TP53-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 1026335). This missense change has been observed in individuals with clinical features of Li Fraumeni syndrome and/or clinical features of Li-Fraumeni syndrome (PMID: 27545002, 29070607, 32658383). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 159 of the TP53 protein (p.Ala159Asp).
Myriad Genetics, Inc. RCV004035219 SCV004931798 likely pathogenic Li-Fraumeni syndrome 1 2024-02-14 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 29070607].
Laboratory of Virology, Oncology, Biosciences and Environment, Faculty of Sciences and Techniques, Mohammedia- University Hassan II of Casablanca RCV003483816 SCV004232138 uncertain significance Prostate cancer, hereditary, 1 2024-01-01 no assertion criteria provided clinical testing

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