ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1032G>C (p.Gln344His)

gnomAD frequency: 0.00002  dbSNP: rs375799148
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163983 SCV000214583 likely benign Hereditary cancer-predisposing syndrome 2023-03-20 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.
Invitae RCV000473165 SCV000548218 benign Hereditary nonpolyposis colorectal neoplasms 2023-08-17 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000163983 SCV000684894 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-24 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 344 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been detected in an individual affected with pediatric low-grade gloma (PMID: 26580448). This variant has been identified in 4/251438 chromosomes 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.
Baylor Genetics RCV003462124 SCV004196230 uncertain significance Lynch syndrome 1 2023-09-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003995306 SCV004824598 uncertain significance Lynch syndrome 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 344 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been detected in an individual affected with pediatric low-grade gloma (PMID: 26580448). This variant has been identified in 4/251438 chromosomes 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.

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