ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2006G>T (p.Gly669Val) (rs63751640)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076356 SCV000107382 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Variant causes splicing aberration (full inactivation of variant allele)
Ambry Genetics RCV000491447 SCV000580412 pathogenic Hereditary cancer-predisposing syndrome 2018-04-13 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Functionally-validated splicing mutation;Other strong data supporting pathogenic classification;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000692084 SCV000819891 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-11-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 669 of the MSH2 protein (p.Gly669Val). 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 been reported in many individuals and families affected with Lynch syndrome in the literature (PMID: 27629256), Universal Mutation Database (PMID: 10612827), and Leiden Open-source Variation Database (PMID: 21520333). In addition, this variant has been observed to segregate with disease in the affected families (PMID: 27629256, Invitae). ClinVar contains an entry for this variant (Variation ID: 90854). Experimental studies using patient RNA and minigene assays have shown that this missense change results in partial or complete exclusion of exon 13, creating a premature translational stop signal (PMID: 27629256, 26247049). In addition, in vitro mismatch repair (MMR) activity assays have shown that this variant results in deficient repair activity (PMID: 27628256). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000581599 SCV000691909 uncertain significance not specified no assertion criteria provided clinical testing

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