ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.722C>A (p.Ser241Tyr)

dbSNP: rs28934573
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053974 SCV001218265 pathogenic Li-Fraumeni syndrome 2024-10-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 241 of the TP53 protein (p.Ser241Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Li-Fraumeni syndrome (PMID: 23259501, 25584008, 28279309, 32817165). ClinVar contains an entry for this variant (Variation ID: 376663). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 25584008, 30224644). This variant disrupts the p.Ser241 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1565143, 23031740, 26911350, 28975465). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001576591 SCV001803812 pathogenic not provided 2023-03-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression ability, and reduced colony formation (Wasserman et al., 2015; Buzby et al., 2017; Giacomelli et al., 2018; Kotler et al., 2018); This variant is associated with the following publications: (PMID: 29979965, 28279309, 28604461, 21601526, 27501770, 25584008, 29070607, 23259501, 30224644, 30840781, 30720243, 32817165, 15510160)
Genome-Nilou Lab RCV002289539 SCV002582471 pathogenic Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002289538 SCV002583131 pathogenic Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV002289538 SCV004932115 likely pathogenic Li-Fraumeni syndrome 1 2024-02-16 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 25584008]. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 23259501, 25584008, 1565143, 20586629].
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785454 SCV000924026 likely pathogenic Ovarian neoplasm 2018-12-01 no assertion criteria provided research

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