ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1893A>T (p.Arg631Ser)

dbSNP: rs747805096
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220090 SCV000276199 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-07 criteria provided, single submitter clinical testing The p.R631S variant (also known as c.1893A>T), located in coding exon 12 of the MSH2 gene, results from an A to T substitution at nucleotide position 1893. The arginine at codon 631 is replaced by serine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. This amino acid position is 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 p.R631S remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000220090 SCV001736385 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-02 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 631 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). 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 1/251464 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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