ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.-6G>C (rs745424307)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572771 SCV000662653 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-03 criteria provided, single submitter clinical testing The p.P3R variant (also known as c.8C>G), located in coding exon 1 of the MUTYH gene, results from a C to G substitution at nucleotide position 8. The proline at codon 3 is replaced by arginine, 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.
Invitae RCV000695272 SCV000823760 uncertain significance MYH-associated polyposis 2018-06-27 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 3 of the MUTYH protein (p.Pro3Arg). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs745424307, ExAC 0.02%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 480012). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 RCV000572771 SCV001734322 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-21 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 3 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 17/249188 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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