Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166002 | SCV000216761 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-30 | criteria provided, single submitter | clinical testing | The p.P470L variant (also known as c.1409C>T), located in coding exon 14 of the MUTYH gene, results from a C to T substitution at nucleotide position 1409. The proline at codon 470 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001762383 | SCV001991019 | uncertain significance | not provided | 2019-05-23 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
| Labcorp Genetics |
RCV003765038 | SCV004685635 | uncertain significance | Familial adenomatous polyposis 2 | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 470 of the MUTYH protein (p.Pro470Leu). This variant is not present in population databases (gnomAD no frequency). 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: 186410). 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. 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. |
| All of Us Research Program, |
RCV003765038 | SCV004825902 | uncertain significance | Familial adenomatous polyposis 2 | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 470 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV003765038 | SCV005056093 | uncertain significance | Familial adenomatous polyposis 2 | 2023-11-11 | criteria provided, single submitter | clinical testing |