ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.6C>T (p.Ala2=) (rs876659248)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217729 SCV000275494 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-31 criteria provided, single submitter clinical testing The c.-4G>A variant located in the 5' untranslated region (5’ UTR) of the MUTYH gene. This variant results from a G to A substitution 4 bases upstream from the first translated codon. This nucleotide position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001705215 SCV000293194 uncertain significance not provided 2019-07-22 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge; Describes a nucleotide substitution 4 base pairs upstream of the ATG translational start site of the MUTYH gene, occurring in the Kozak sequence, the conserved nucleotides just upstream of the ATG start codon, which play a major role in the initiation of translation
Color Health, Inc RCV000217729 SCV001353232 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000236456 SCV001363473 uncertain significance not specified 2019-09-12 criteria provided, single submitter clinical testing Variant summary: MUTYH c.-4G>A is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 4e-06 in 249050 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-4G>A in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014) and cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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