ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2048G>A (p.Gly683Glu) (rs755920849)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000579644 SCV000685004 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing
Invitae RCV000689059 SCV000816696 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 683 of the MSH2 protein (p.Gly683Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 489931). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The p.Gly683 amino acid residue in MSH2 has been determined to be clinically significant (PMID: 18931482, 11606497, 19731080, 26248088, 23690608, 23690608). This suggests that variants that disrupt this residue are likely to be causative of disease. 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.

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