Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004605053 | SCV005100585 | uncertain significance | Inborn genetic diseases | 2024-04-27 | criteria provided, single submitter | clinical testing | The p.E195V variant (also known as c.584A>T), located in coding exon 3 of the ACD gene, results from an A to T substitution at nucleotide position 584. The glutamic acid at codon 195 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV003818923 | SCV004613281 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 195 of the ACD protein (p.Glu195Val). This variant is present in population databases (rs770621727, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACD protein function with a positive predictive value of 80%. 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. |