Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000215169 | SCV000278416 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-16 | 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 Diagnostics, |
RCV000215169 | SCV000914017 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000818843 | SCV000959477 | uncertain significance | Familial adenomatous polyposis 2 | 2023-05-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 233944). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3 of the MUTYH protein (p.Pro3Leu). |