Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486456 | SCV000573816 | likely pathogenic | not provided | 2022-08-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed with a pathogenic variant on the opposite allele (in trans) in a patient with clinical features consistent with ADAR-related Aicardi-Goutieres syndrome in published literature (Samanta et al., 2019); This variant is associated with the following publications: (PMID: 30692772) |
| Invitae | RCV000805404 | SCV000945358 | uncertain significance | Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6 | 2022-09-09 | 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 ADAR protein function. ClinVar contains an entry for this variant (Variation ID: 424040). This missense change has been observed in individual(s) with ADAR-related conditions (PMID: 30692772). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1193 of the ADAR protein (p.Glu1193Lys). |