ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1276C>T (p.Gln426Ter) (rs63750316)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075164 SCV000106155 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000571335 SCV000676029 pathogenic Hereditary cancer-predisposing syndrome 2016-12-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000571335 SCV000689799 pathogenic Hereditary cancer-predisposing syndrome 2017-07-05 criteria provided, single submitter clinical testing
Invitae RCV000690382 SCV000818066 pathogenic Hereditary nonpolyposis colon cancer 2018-05-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln426*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with colorectal cancer, medulloblastoma and suspected of Lynch syndrome (PMID: 12112654, 28944238, 28874130, 24344984, 25648859, 26437257,24090359). ClinVar contains an entry for this variant (Variation ID: 89691). Experimental studies have shown that this nonsense change (p.Gln426*) results in inability to form complexes with hEXO1 and hPMS2 in vivo (PMID: 11429708). Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000075164 SCV000838012 pathogenic Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000075164 SCV000914320 pathogenic Lynch syndrome 2019-01-30 criteria provided, single submitter research

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