Submissions for variant NM_000251.3(MSH2):c.982G>A (p.Ala328Thr)

dbSNP: rs753237286

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000457800	SCV000548322	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-09-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000575104	SCV000669820	likely benign	Hereditary cancer-predisposing syndrome	2021-12-29	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.
Counsyl	RCV000663211	SCV000786395	uncertain significance	Lynch syndrome 1	2018-04-24	criteria provided, single submitter	clinical testing
Service de Génétique Médicale, Institut Central des Hôpitaux	RCV000852299	SCV000994924	uncertain significance	Lynch syndrome	2019-04-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000575104	SCV001346976	uncertain significance	Hereditary cancer-predisposing syndrome	2019-10-24	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 328 of the MSH2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx	RCV001584155	SCV001812692	uncertain significance	not provided	2021-05-27	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Myriad Genetics, Inc.	RCV000663211	SCV004018238	uncertain significance	Lynch syndrome 1	2023-03-16	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV000852299	SCV004824509	uncertain significance	Lynch syndrome	2023-11-30	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 328 of the MSH2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.