ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.143A>C (p.Gln48Pro) (rs587778914)

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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) RCV000075213 SCV000106205 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability 0.95-0.99
Invitae RCV001069994 SCV001235200 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-12-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 48 of the MLH1 protein (p.Gln48Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Lynch syndrome (PMID: 22395473, 21404117). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 89739). This variant has been reported to affect MLH1 protein function (PMID: 21404117). For these reasons, this variant has been classified as Pathogenic.

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