Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001905891 | SCV002152347 | uncertain significance | Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6 | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 654 of the ADAR protein (p.Ala654Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ADAR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1386880). 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 ADAR protein function. |
| Ambry Genetics | RCV004611952 | SCV005105998 | uncertain significance | Inborn genetic diseases | 2024-06-07 | criteria provided, single submitter | clinical testing | The c.1960G>A (p.A654T) alteration is located in exon 5 (coding exon 5) of the ADAR gene. This alteration results from a G to A substitution at nucleotide position 1960, causing the alanine (A) at amino acid position 654 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |