Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026746 | SCV001189184 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-02 | criteria provided, single submitter | clinical testing | The p.L257R variant (also known as c.770T>G), located in coding exon 9 of the MUTYH gene, results from a T to G substitution at nucleotide position 770. The leucine at codon 257 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly 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 | RCV001037758 | SCV001201187 | uncertain significance | Familial adenomatous polyposis 2 | 2022-05-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 827215). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 257 of the MUTYH protein (p.Leu257Arg). |