ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.178T>C (p.Leu60=) (rs35819209)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080064 SCV000166214 benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000212625 SCV000170366 benign not specified 2014-03-03 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 RCV000126838 SCV000214176 likely benign Hereditary cancer-predisposing syndrome 2015-01-06 criteria provided, single submitter clinical testing
Counsyl RCV000412370 SCV000488979 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-07-29 criteria provided, single submitter clinical testing
Color RCV000126838 SCV000537511 likely benign Hereditary cancer-predisposing syndrome 2015-12-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212625 SCV000601516 likely benign not specified 2017-02-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679218 SCV000805849 likely benign not provided 2017-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679218 SCV000889459 likely benign not provided 2018-05-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212625 SCV001362734 likely benign not specified 2019-03-01 criteria provided, single submitter clinical testing Variant summary: MSH6 c.178T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.4e-05 in 157094 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MSH6 causing Lynch Syndrome (6.4e-05 vs 0.00014), allowing no conclusion about variant significance. c.178T>C has been reported in the literature in individuals affected with colon cancer. This report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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