Submissions for variant NM_000546.6(TP53):c.645T>G (p.Ser215Arg)

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Total submissions: 8

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV006273745	SCV007129864	oncogenic	Neoplasm	2025-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV004786685	SCV005401443	likely pathogenic	not provided	2024-05-15	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12826609, 29979965, 34273903, 26619011, 30224644, 30287823, 36243179, 35659507, 32164171, 15510160, 33309985, 32980694, 30840781)
Myriad Genetics, Inc.	RCV000662560	SCV004017846	likely pathogenic	Li-Fraumeni syndrome 1	2023-04-11	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].
Genome-Nilou Lab	RCV000662560	SCV002582562	uncertain significance	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002289537	SCV002582034	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000465501	SCV000545340	pathogenic	Li-Fraumeni syndrome	2026-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 215 of the TP53 protein (p.Ser215Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376661). 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%. For these reasons, this variant has been classified as Pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785463	SCV000924035	likely pathogenic	Ovarian neoplasm	2018-12-01	no assertion criteria provided	research
Counsyl	RCV000662560	SCV000785159	uncertain significance	Li-Fraumeni syndrome 1	2017-05-10	no assertion criteria provided	clinical testing	This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

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