ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.-6G>A (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 RCV000215169 SCV000278416 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-11 criteria provided, single submitter clinical testing The p.P3L variant (also known as c.8C>T), located in coding exon 1 of the MUTYH gene, results from a C to T substitution at nucleotide position 8. The proline at codon 3 is replaced by leucine, an amino acid with similar 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.
Color Health, Inc RCV000215169 SCV000914017 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-30 criteria provided, single submitter clinical testing
Invitae RCV000818843 SCV000959477 uncertain significance MYH-associated polyposis 2019-04-04 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 3 of the MUTYH protein (p.Pro3Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 233944). 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 leucine 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.

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