ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1837A>C (p.Asn613His) (rs200147804)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705544 SCV000834545 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-03-26 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 613 of the MSH2 protein (p.Asn613His). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is present in population databases (rs200147804, ExAC 0.03%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 41647). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000771463 SCV000903891 likely benign Hereditary cancer-predisposing syndrome 2016-05-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000771463 SCV001173877 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-11 criteria provided, single submitter clinical testing The p.N613H variant (also known as c.1837A>C), located in coding exon 12 of the MSH2 gene, results from an A to C substitution at nucleotide position 1837. The asparagine at codon 613 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034555 SCV000043345 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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