ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.586C>T (p.Pro196Ser)

dbSNP: rs587782804
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132363 SCV000187453 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-18 criteria provided, single submitter clinical testing The p.P196S variant (also known as c.586C>T), located in coding exon 3 of the MSH2 gene, results from a C to T substitution at nucleotide position 586. The proline at codon 196 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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.
Invitae RCV000629706 SCV000750662 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-09-30 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000132363 SCV001342618 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-20 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 196 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). 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 1/251372 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.
All of Us Research Program, National Institutes of Health RCV003998144 SCV004830728 uncertain significance Lynch syndrome 2023-03-04 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 196 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251372 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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