ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1875C>T (p.Ser625=) (rs63749886)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074695 SCV000107899 likely benign Lynch syndrome 2018-10-18 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability 0.001-0.049 (0.029)
Ambry Genetics RCV000162760 SCV000213237 likely benign Hereditary cancer-predisposing syndrome 2015-01-22 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.
Invitae RCV001084121 SCV000252626 benign Hereditary nonpolyposis colorectal neoplasms 2020-11-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000074695 SCV000430965 uncertain significance Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000504553 SCV000601522 likely benign not specified 2017-05-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162760 SCV000690231 benign Hereditary cancer-predisposing syndrome 2015-10-29 criteria provided, single submitter clinical testing
Counsyl RCV000663035 SCV000786072 likely benign Hereditary nonpolyposis colorectal cancer type 5 2018-02-23 criteria provided, single submitter clinical testing
Mendelics RCV000074695 SCV000837890 likely benign Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759847 SCV000889463 likely benign not provided 2019-09-12 criteria provided, single submitter clinical testing
Mendelics RCV000663035 SCV001135812 likely benign Hereditary nonpolyposis colorectal cancer type 5 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000504553 SCV001361761 likely benign not specified 2020-11-06 criteria provided, single submitter clinical testing
GeneDx RCV000759847 SCV001884172 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353534 SCV000592593 benign Carcinoma of colon no assertion criteria provided clinical testing The p.Ser625Ser variant was identified by Vahteristo, 2005 in a breast or colorectal carcinoma patient with family history of cancer. The variant was also identified in dbSNP (ID: rs63749886) “With uncertain significance”, “Mismatch Repair Genes Variant Database”, “Zhejiang Colon Cancer Database”, the ClinVar database 1x with “uncertain significance”, InSiGHT Colon Cancer Gene Variant Database 1X as an “unknown variant” and UMD 1 X as a “neutral” variant,. This variant was also identified in the the Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014) in 19 of 120346 (European (Finnish and non-Finnish) and Latino) alleles (frequency: 0.00016), although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Ser625Ser 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. In addition, this variant was found in our laboratory to co-occur in with a known pathogenic variant c.3957dupA, increasing the likelihood that this variant does not have clinical significance. In summary, based on the above information, this variant meets our laboratories criteria to be classified as benign.

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