ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.204del (p.Pro69fs) (rs63750199)

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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) RCV000076373 SCV000107400 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000491774 SCV000580610 pathogenic Hereditary cancer-predisposing syndrome 2015-10-15 criteria provided, single submitter clinical testing
GeneDx RCV000657242 SCV000778971 pathogenic not provided 2017-11-22 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH2 is denoted c.204delG at the cDNA level and p.Pro69ArgfsX15 (P69RfsX15) at the protein level. The normal sequence, with the base that is deleted in brackets, is TGGG[delG]CCGG. The deletion causes a frameshift which changes a Proline to an Arginine at codon 69, and creates a premature stop codon at position 15 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.204delG reportedly segregated with disease in a family fulfilling Amsterdam criteria, with a history of colorectal and endometrial cancer (Wahlberg 1997). We consider this variant to be pathogenic.
Invitae RCV001210613 SCV001382109 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-09-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro69Argfs*15) 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 affected with clinical features of Lynch syndrome (PMID: 9036882, 25430799). This variant is also known as c.201delG in the literature. ClinVar contains an entry for this variant (Variation ID: 90871). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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