ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3160A>T (p.Ile1054Phe) (rs267608075)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115403 SCV000172809 likely benign Hereditary cancer-predisposing syndrome 2017-12-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Color RCV000115403 SCV000910609 benign Hereditary cancer-predisposing syndrome 2015-12-09 criteria provided, single submitter clinical testing
GeneDx RCV000200988 SCV000149312 likely benign not specified 2017-12-22 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.
Integrated Genetics/Laboratory Corporation of America RCV000200988 SCV000695841 likely benign not specified 2018-10-08 criteria provided, single submitter clinical testing MSH6 c.3160A>T (p.Ile1054Phe) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, core domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 272594 control chromosomes (gnomAD). The observed variant frequency is approximately 1.19 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 benign. c.3160A>T has been reported in the literature in individuals affected with Lynch Syndrome (Grant_2015, Pal_2012, Steinke_2008). These report(s) do 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. Four ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as likely benign.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074806 SCV000108017 likely benign Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability 0.001-0.049
Invitae RCV000524155 SCV000218996 benign Hereditary nonpolyposis colon cancer 2018-01-05 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000586516 SCV000778622 likely benign not provided 2017-11-10 no assertion criteria provided clinical testing
Mendelics RCV000074806 SCV000837909 likely benign Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586516 SCV000889484 likely benign not provided 2017-10-11 criteria provided, single submitter clinical testing

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