ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1901G>T (p.Gly634Val) (rs786202396)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165186 SCV000215898 uncertain significance Hereditary cancer-predisposing syndrome 2014-08-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000554358 SCV000625108 uncertain significance Hereditary nonpolyposis colon cancer 2017-07-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 634 of the MLH1 protein (p.Gly634Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 185711). 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. 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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