ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.786G>T (p.Glu262Asp) (rs754820584)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473312 SCV000548178 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 262 of the MSH2 protein (p.Glu262Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH2-related disease. 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. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000587461 SCV000696282 uncertain significance not provided 2017-08-21 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.786G>T (p.Glu262Asp) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 120372 control chromosomes. One clinical diagnostic laboratory/reputable database classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
PreventionGenetics,PreventionGenetics RCV000587461 SCV000806047 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV001026892 SCV001189364 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-04 criteria provided, single submitter clinical testing Insufficient evidence

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