Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000430091 | SCV000529600 | uncertain significance | not provided | 2016-07-04 | criteria provided, single submitter | clinical testing | The H133D variant in the ACD gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The H133D variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H133D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret H133D as a variant of uncertain significance. |
| Labcorp Genetics |
RCV003766336 | SCV004678515 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-02-03 | 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. 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 not expected to disrupt ACD protein function. ClinVar contains an entry for this variant (Variation ID: 387524). This variant has not been reported in the literature in individuals affected with ACD-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 133 of the ACD protein (p.His133Asp). |
| Ambry Genetics | RCV004601167 | SCV005100621 | uncertain significance | Inborn genetic diseases | 2024-05-20 | criteria provided, single submitter | clinical testing | The p.H133D variant (also known as c.397C>G), located in coding exon 2 of the ACD gene, results from a C to G substitution at nucleotide position 397. The histidine at codon 133 is replaced by aspartic acid, an amino acid with similar 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. |