ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3399T>C (p.Thr1133=) (rs61748084)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162415 SCV000212754 likely benign Hereditary cancer-predisposing syndrome 2014-08-26 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.
Counsyl RCV000409777 SCV000487809 likely benign Hereditary nonpolyposis colorectal cancer type 5 2015-11-17 criteria provided, single submitter clinical testing
Invitae RCV000458051 SCV000561535 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162415 SCV000690349 likely benign Hereditary cancer-predisposing syndrome 2016-04-04 criteria provided, single submitter clinical testing
GeneDx RCV000610158 SCV000729047 benign not specified 2015-05-21 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000610158 SCV000919734 likely benign not specified 2019-08-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357664 SCV001553194 likely benign not provided no assertion criteria provided clinical testing The MSH6 p.Thr1133= variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (ID: rs61748084) as "With Likely benign allele", and in ClinVar (classified as benign by GeneDx; as likely benign by Invitae, Ambry Genetics, Counsyl and Color). The variant was identified in control databases in 9 of 277182 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 24036 chromosomes (freq: 0.00004), Latino in 1 of 34408 chromosomes (freq: 0.00003), European in 7 of 126686 chromosomes (freq: 0.00006); it was not observed in the Other, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Thr1133= 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) do not predict a difference in splicing. 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 likely benign.

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