ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2239C>T (p.Leu747=) (rs63751305)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001081616 SCV000166217 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000212662 SCV000170355 benign not specified 2014-05-12 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.
Ambry Genetics RCV000126828 SCV000213307 likely benign Hereditary cancer-predisposing syndrome 2015-01-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Health, Inc RCV000126828 SCV000690249 likely benign Hereditary cancer-predisposing syndrome 2015-07-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000656571 SCV000805858 likely benign not provided 2017-09-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212662 SCV001362790 likely benign not specified 2019-09-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354018 SCV000592601 likely benign Lynch syndrome no assertion criteria provided clinical testing The p.Leu747Leu variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified by Woods (2005) in the proband of a Lynch syndrome-like family; the prevalence of the variant in a control group was not included in the published data. The variant was identified at very low frequencies (<0.0001 – 0.00015) in three populations in the Exome Aggregation Consortium (ExAC) database: European (Finnish), European (Non-Finnish), and African). These low frequencies are not substantive enough to comment on the variant’s relationship to disease.The variant was identified in the UMD (1X as an unclassified variant), “Mismatch Repair Genes Variant Database”, InSiGHT Colon Cancer Gene Variant Database, the ClinVar database (classified as benign by GeneDX, classified as likely benign by Invitae and Ambry Genetics, classified with uncertain significance by InSiGHT). In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000656571 SCV000778619 likely benign not provided 2017-11-16 no assertion criteria provided clinical testing

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