Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019783 | SCV001181187 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-23 | criteria provided, single submitter | clinical testing | The p.L11R variant (also known as c.32T>G), located in coding exon 1 of the MUTYH gene, results from a T to G substitution at nucleotide position 32. The leucine at codon 11 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other 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. |
| Gene |
RCV001766848 | SCV002001079 | uncertain significance | not provided | 2020-06-02 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge; Protein-based in silico analysis supports a deleterious effect. In addition, splice predictors suggest this variant may impact gene splicing. In the absence of RNA or functional studies, the actual effect of this sequence change is unknown. |
| Invitae | RCV002551820 | SCV002956039 | uncertain significance | Familial adenomatous polyposis 2 | 2023-07-14 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 11 of the MUTYH protein (p.Leu11Arg). This variant is present in population databases (rs752665489, gnomAD 0.006%). 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: 823495). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |