ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.739T>C (p.Ser247Pro) (rs63750948)

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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) RCV000075833 SCV000106847 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability >0.99
Invitae RCV000629770 SCV000750726 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 247 of the MLH1 protein (p.Ser247Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals and families affected with Lynch syndrome (PMID: 12200596, 22736432, 16083711, 16216036, 15849733, 27435373). ClinVar contains an entry for this variant (Variation ID: 90342). Experimental studies have shown that this missense change affects MLH1 protein expression, cellular localization, and impairs mismatch repair activity (PMID: 16083711, 17594722). 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.
Color RCV001183309 SCV001349014 likely pathogenic Hereditary cancer-predisposing syndrome 2018-12-27 criteria provided, single submitter clinical testing

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