Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001048319 | SCV001212318 | uncertain significance | Familial adenomatous polyposis 2 | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 243 of the MUTYH protein (p.Leu243Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of familial attenuated adenomatous polyposis (PMID: 10612827; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 845282). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV002379534 | SCV002672920 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-16 | criteria provided, single submitter | clinical testing | The p.L243P variant (also known as c.728T>C), located in coding exon 9 of the MUTYH gene, results from a T to C substitution at nucleotide position 728. The leucine at codon 243 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |