ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.576C>G (p.Ile192Met)

dbSNP: rs864622381
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000702160 SCV000831001 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-03 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001175679 SCV001339369 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 192 of the MSH2 protein. Computational prediction 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). 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). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has been identified in 1/251432 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.
Ambry Genetics RCV001175679 SCV002650748 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-13 criteria provided, single submitter clinical testing The p.I192M variant (also known as c.576C>G), located in coding exon 3 of the MSH2 gene, results from a C to G substitution at nucleotide position 576. The isoleucine at codon 192 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003460973 SCV004196930 uncertain significance Lynch syndrome 1 2021-10-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999726 SCV004828444 uncertain significance Lynch syndrome 2023-09-04 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 192 of the MSH2 protein. Computational prediction 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). 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). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has been identified in 1/251432 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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