ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1897A>G (p.Ile633Val) (rs771695599)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163067 SCV000213563 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000168408 SCV000219102 uncertain significance Hereditary nonpolyposis colon cancer 2018-01-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 633 of the MSH2 protein (p.Ile633Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs771695599, ExAC 0.01%). This variant has been reported in an individual undergoing genetic testing for Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 183977). 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 valine 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. 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.
Counsyl RCV000662475 SCV000784971 uncertain significance Lynch syndrome I 2017-02-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759104 SCV000888210 uncertain significance not provided 2017-12-11 criteria provided, single submitter clinical testing

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