Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000804680 | SCV000944600 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2018-12-04 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ACD-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 331 of the ACD protein (p.Arg331Lys). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and lysine. |
| Ambry Genetics | RCV004028188 | SCV005037470 | uncertain significance | Inborn genetic diseases | 2023-10-11 | criteria provided, single submitter | clinical testing | The p.R331K variant (also known as c.992G>A), located in coding exon 8 of the ACD gene, results from a G to A substitution at nucleotide position 992. The arginine at codon 331 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |