ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1550_1551CA[1] (p.Gln518fs) (rs63749930)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076193 SCV000107209 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
GeneDx RCV000235817 SCV000293508 pathogenic not provided 2015-12-02 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in MSH2 is denoted c.1552_1553delCA at the cDNA level and p.Gln518ValfsX10(Q518VfsX10) at the protein level. The normal sequence, with the bases that are deleted in braces, is TGCA[CA]GTTT. The deletion causes a frameshift, which changes a Glutamine to a Valine at codon 518, and creates a premature stop codon at position 10 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.1552_1553delCA, also published as MSH2 c.1550_1551delCA, has been reported in several families with Lynch syndrome (Nystrom-Lahti 1996, Holmberg 1998, Liu 1998, Gylling 2008, Yan 2008, Peltomaki 2001, Schweizer 2001, Cederquist 2004). We consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076193 SCV000592506 pathogenic Lynch syndrome criteria provided, single submitter clinical testing
Invitae RCV000707356 SCV000836450 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-09-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln518Valfs*10) 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 reported in several families affected with hereditary non-polyposis colorectal cancer (PMID: 8776590, 11306449, 18307539, 14961575, 11304573). This variant is also known as MSH2 c.1550_1551delCA in the literature. ClinVar contains an entry for this variant (Variation ID: 90697). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235817 SCV001134340 pathogenic not provided 2019-02-12 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Color RCV001187673 SCV001354535 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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