ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.910A>G (p.Ile304Val)

dbSNP: rs1558464351
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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 RCV000698160 SCV000826804 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-01-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 304 of the MSH2 protein (p.Ile304Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. 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 (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. This variant has not been reported in the literature in individuals with MSH2-related disease. This variant is not present in population databases (ExAC no frequency).
Color Diagnostics, LLC DBA Color Health RCV003584721 SCV004356641 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-20 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 304 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 not been identified 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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