Submissions for variant NM_002439.5(MSH3):c.1469C>A (p.Ser490Tyr)

gnomAD frequency: 0.00201  dbSNP: rs76249824

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000919708	SCV001065062	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001011727	SCV001172084	likely benign	Hereditary cancer-predisposing syndrome	2018-12-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genetic Services Laboratory, University of Chicago	RCV001818866	SCV002071556	likely benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000919708	SCV002499781	uncertain significance	not provided	2025-03-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with colorectal cancer (PMID: 28944238); This variant is associated with the following publications: (PMID: 28944238)
Sema4, Sema4	RCV001011727	SCV002535958	likely benign	Hereditary cancer-predisposing syndrome	2021-07-03	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005359664	SCV005921210	uncertain significance	Familial adenomatous polyposis 4	2024-01-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003913088	SCV004734955	likely benign	MSH3-related disorder	2021-11-12	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).