ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1046C>G (p.Pro349Arg) (rs587779067)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000490568 SCV000107019 pathogenic Lynch syndrome I 2014-10-10 reviewed by expert panel research Multifactorial likelihood analysis posterior probability >0.99
Invitae RCV000076008 SCV000548140 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-08-03 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 349 of the MSH2 protein (p.Pro349Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several families affected with Lynch syndrome (PMID: 21239990, 27606285, 24278394). ClinVar contains an entry for this variant (Variation ID: 90513). An experimental study has shown that this missense change destabilizes the MSH2 protein and disrupts its mismatch repair activity in vitro (PMID: 26951660). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000490568 SCV000677754 likely pathogenic Lynch syndrome I 2016-11-15 criteria provided, single submitter clinical testing

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