ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1022T>C (p.Leu341Pro) (rs63751147)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076002 SCV000107012 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability 0.95-0.99
Invitae RCV001213427 SCV001385056 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-07-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 341 of the MSH2 protein (p.Leu341Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Lynch syndrome (PMID: 12624141). ClinVar contains an entry for this variant (Variation ID: 90507). Based on a multifactorial likelihood algorithm using genetic data, this variant has been determined to have a high probability of being pathogenic (PMID: 24362816). This variant has been reported to affect MSH2 protein function (PMID: 26951660). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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