ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.885-5G>T (rs267607802)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160558 SCV000216095 likely benign Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intronic alteration with no splicing impact by rt-pcr analysis or other splicing assay
Color RCV000160558 SCV000684879 benign Hereditary cancer-predisposing syndrome 2016-03-04 criteria provided, single submitter clinical testing
GeneDx RCV000417381 SCV000211137 likely benign not specified 2017-09-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000585990 SCV000696187 likely benign not provided 2016-05-16 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.885-5G>T variant involves the alteration of a non-conserved intronic nucleotide. 3/5 splice prediction tools predict no significant impact on normal splicing. Functional analysis using the pCAS ex vivo splicing assay and RNA analysis demonstrated this variant had no effect (Tournier_2008), strongly supporting for benign outcome. This variant was found in 2/121336 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic MLH1 variant (0.0007105). However, the population data could still suggest it to be a rare polymorphism. It has been reported in one HNPCC family in literature without strong evidence for or against pathogenicity (Parc_2003). Multiple clinical labs as well as a reputable database has classified it as likely benign/neutral. Taken together, this variant has currently been classified as Likely Benign..
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075917 SCV000106936 likely benign Lynch syndrome 2013-09-05 reviewed by expert panel research Intronic substitution with no effect on splicing, tested with NMD inhibitor
Invitae RCV000524320 SCV000253145 likely benign Hereditary nonpolyposis colon cancer 2017-09-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000417381 SCV000601414 likely benign not specified 2017-06-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000585990 SCV000889408 likely benign not provided 2017-06-08 criteria provided, single submitter clinical testing

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