ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.387_388delTC (rs63750924)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076591 SCV000107624 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000684791 SCV000255276 pathogenic Hereditary nonpolyposis colon cancer 2018-06-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln130Valfs*2) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals (PMID: 28514183, 15849733, 10375096) and several families affected with Lynch syndrome (PMID: 8592341, 12658575). This variant is also known as 129delTC or c.388_389delTC in the literature. ClinVar contains an entry for this variant (Variation ID: 91089). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000202145 SCV000292615 pathogenic not provided 2015-09-16 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in MSH2 is denoted c.387_388delTC at the cDNA level and p.Gln130ValfsX2 (Q130VfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is TCTC[TC]AGTT. The deletion causes a frameshift, which changes a Glutamine to a Valine at codon 130, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH2 c.387_388delTC, also known as 129delTC or c.388_389delTC using alternative nomenclature, has been observed in several individuals with personal and/or family histories consistent with Lynch syndrome (Buerstedde 1995, Wagner 2003, Mangold 2005). We consider this variant to be pathogenic.
Ambry Genetics RCV000491648 SCV000580392 pathogenic Hereditary cancer-predisposing syndrome 2017-09-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076591 SCV000592464 pathogenic Lynch syndrome 2012-07-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202145 SCV000601476 pathogenic not provided 2015-09-11 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202145 SCV000257188 pathogenic not provided no assertion criteria provided clinical testing

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