ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.250A>G (p.Lys84Glu) (rs63750641)

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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) RCV000075606 SCV000106603 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Abrogated function & >2 MSI-H tumours
Invitae RCV001201354 SCV000543580 likely pathogenic Hereditary nonpolyposis colon cancer 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 84 of the MLH1 protein (p.Lys84Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals with clinical features of Lynch syndrome (PMID: 19419416, 10323887, 26053027, 17453009, 21404117). ClinVar contains an entry for this variant (Variation ID: 90120). This variant has been reported to affect MLH1 protein function (PMID: 21404117, 17510385, 23403630, 15475387, 16083711, 12513688). Based on a multifactorial likelihood algorithm using genetic, clinical, in silico and functional data, this variant has been determined to have a high probability of being pathogenic (PMID: 24362816). 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000075606 SCV000592342 likely pathogenic Lynch syndrome 2012-07-14 criteria provided, single submitter clinical testing

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