ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2904C>G (p.Val968=) (rs150683226)

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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 RCV000163540 SCV000214098 likely benign Hereditary cancer-predisposing syndrome 2015-06-03 criteria provided, single submitter clinical testing
Invitae RCV001086343 SCV000283771 likely benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000411849 SCV000488555 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-05-03 criteria provided, single submitter clinical testing
GeneDx RCV000440970 SCV000513695 benign not specified 2015-07-13 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.
Color RCV000163540 SCV000685330 likely benign Hereditary cancer-predisposing syndrome 2017-02-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759854 SCV000889476 likely benign not provided 2018-05-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000440970 SCV000917789 benign not specified 2018-12-20 criteria provided, single submitter clinical testing Variant summary: MSH6 c.2904C>G 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 0.00012 in 239046 control chromosomes, predominantly at a frequency of 0.00026 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Lynch Syndrome phenotype (0.00014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.2904C>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five 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 benign.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000440970 SCV000691935 likely benign not specified no assertion criteria provided clinical testing

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