ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.-15G>T (rs587782837)

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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 RCV000132425 SCV000187518 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-05 criteria provided, single submitter clinical testing The p.S6Y variant (also known as c.17C>A), located in coding exon 1 of the MUTYH gene, results from a C to A substitution at nucleotide position 17. The serine at codon 6 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000656906 SCV000211397 uncertain significance not provided 2019-08-19 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in at least one individual who had multigene hereditary cancer panel testing (Mu 2016); This variant is associated with the following publications: (PMID: 27720647)
Invitae RCV000458224 SCV000545760 uncertain significance MYH-associated polyposis 2020-10-08 criteria provided, single submitter clinical testing This sequence change replaces serine with tyrosine at codon 6 of the MUTYH protein (p.Ser6Tyr). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is present in population databases (rs587782837, ExAC 0.05%). This variant has been observed in an individual affected with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 142941). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000132425 SCV000685602 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-11 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000656906 SCV000806352 uncertain significance not provided 2017-05-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212695 SCV000919798 uncertain significance not specified 2018-07-13 criteria provided, single submitter clinical testing Variant summary: MUTYH c.17C>A (p.Ser6Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.8e-05 in 275598 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MUTYH causing Hereditary Breast and Ovarian Cancer (9.8e-05 vs 0.0056) allowing no conclusion about variant significance. The variant, c.17C>A, has been reported in the literature in individuals affected with MUTYH-associated Polyposis (Tung_2014). These report(s) do not provide unequivocal conclusions about association of the variant with MUTYH-associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656906 SCV001470569 uncertain significance not provided 2020-02-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000458224 SCV001481434 uncertain significance MYH-associated polyposis 2019-03-06 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic RCV000212695 SCV000691954 uncertain significance not specified no assertion criteria provided clinical testing

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