ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1311G>T (p.Val437=) (rs730881781)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160645 SCV000211247 benign not specified 2014-07-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl RCV000412435 SCV000488392 likely benign Lynch syndrome I 2016-03-15 criteria provided, single submitter clinical testing
Invitae RCV000547785 SCV000625248 likely benign Hereditary nonpolyposis colon cancer 2017-06-09 criteria provided, single submitter clinical testing
Color RCV000774566 SCV000908301 likely benign Hereditary cancer-predisposing syndrome 2018-05-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000160645 SCV000919701 uncertain significance not specified 2018-03-30 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1311G>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 1.2e-05 in 245732 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in MSH2 causing Lynch Syndrome (1.2e-05 vs 0.00057), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1311G>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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