Submissions for variant NM_002439.5(MSH3):c.1177G>A (p.Val393Met)

gnomAD frequency: 0.00013  dbSNP: rs761779919

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000936767	SCV001082539	likely benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001010146	SCV001170300	uncertain significance	Hereditary cancer-predisposing syndrome	2024-05-31	criteria provided, single submitter	clinical testing	The p.V393M variant (also known as c.1177G>A), located in coding exon 8 of the MSH3 gene, results from a G to A substitution at nucleotide position 1177. The valine at codon 393 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Sema4, Sema4	RCV001010146	SCV002535929	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-04	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002268368	SCV002550486	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000936767	SCV003836903	uncertain significance	not provided	2024-03-19	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000936767	SCV004221029	likely benign	not provided	2022-12-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003942940	SCV004763475	likely benign	MSH3-related disorder	2022-04-01	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).