ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.143A>C (p.Gln48Pro)

dbSNP: rs587778914
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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) 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 2019-12-19 criteria provided, single submitter clinical testing This variant has been reported to affect MLH1 protein function (PMID: 21404117). 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 is not present in population databases (ExAC no frequency). 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. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003451028 SCV004188487 likely pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-11 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 30504929]. This variant is expected to disrupt protein structure [Myriad internal data].

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