Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001187348 | SCV001354121 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 394 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 MUTYH-related disorders 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. |
Invitae | RCV001224521 | SCV001396723 | uncertain significance | Familial adenomatous polyposis 2 | 2023-03-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 925423). 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 aspartic acid 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 not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 394 of the MUTYH protein (p.Asn394Asp). |
Mendelics | RCV002249770 | SCV002518325 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001187348 | SCV002635276 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-10 | criteria provided, single submitter | clinical testing | The p.N394D variant (also known as c.1180A>G), located in coding exon 12 of the MUTYH gene, results from an A to G substitution at nucleotide position 1180. The asparagine at codon 394 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by BayesDel in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |