ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1798G>A (p.Val600Ile)

dbSNP: rs1580027482
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802725 SCV000942567 uncertain significance not provided 2018-10-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces valine with isoleucine at codon 600 of the MSH3 protein (p.Val600Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH3-related disease.
Ambry Genetics RCV003166219 SCV003861324 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-05 criteria provided, single submitter clinical testing The p.V600I variant (also known as c.1798G>A), located in coding exon 13 of the MSH3 gene, results from a G to A substitution at nucleotide position 1798. The valine at codon 600 is replaced by isoleucine, an amino acid with highly 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.

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