Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002367405 | SCV002662645 | uncertain significance | Inborn genetic diseases | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.C237F variant (also known as c.710G>T), located in coding exon 5 of the ACD gene, results from a G to T substitution at nucleotide position 710. The cysteine at codon 237 is replaced by phenylalanine, an amino acid with highly 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 |
RCV003754955 | SCV004459105 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-04-24 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 1757220). This variant has not been reported in the literature in individuals affected with ACD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 237 of the ACD protein (p.Cys237Phe). 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. |