ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.298C>T (p.Arg100Ter) (rs63751221)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569466 SCV000662011 pathogenic Hereditary cancer-predisposing syndrome 2018-04-26 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),Rarity in general population databases (dbsnp, esp, 1000 genomes),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Color RCV000569466 SCV000689871 pathogenic Hereditary cancer-predisposing syndrome 2017-07-27 criteria provided, single submitter clinical testing
Counsyl RCV000576742 SCV000677732 pathogenic Lynch syndrome II 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000030223 SCV000592344 pathogenic Lynch syndrome 2013-11-27 criteria provided, single submitter clinical testing
GeneDx RCV000220956 SCV000279069 pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.298C>T at the cDNA level and p.Arg100Ter (R100X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in several individuals with personal and family history consistent with Lynch syndrome (Wang 1999, Peel 2000, Hampel 2005, Lagerstedt Robinson 2007, Bruegl 2017) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000030223 SCV000052890 pathogenic Lynch syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030223 SCV000106619 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000524287 SCV000543562 pathogenic Hereditary nonpolyposis colon cancer 2018-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 100 (p.Arg100*) of the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with hereditary non-polyposis colorectal cancer (HNPCC) (PMID: 11606497, 15872200, 17312306) and has been shown to co-segregate with disease in several HPNCC families (PMID: 10480359, 14512394, 15235038) For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000220956 SCV000691844 pathogenic not provided no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000220956 SCV000601394 pathogenic not provided 2015-11-10 criteria provided, single submitter clinical testing

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