Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002437661 | SCV002745914 | uncertain significance | Inborn genetic diseases | 2024-06-06 | criteria provided, single submitter | clinical testing | The p.R96W variant (also known as c.286C>T), located in coding exon 1 of the ACD gene, results from a C to T substitution at nucleotide position 286. The arginine at codon 96 is replaced by tryptophan, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003754990 | SCV004552346 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 96 of the ACD protein (p.Arg96Trp). This variant is present in population databases (rs775787415, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1797036). 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. 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. |