Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001229338 | SCV001401780 | uncertain significance | Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6 | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 215 of the ADAR protein (p.Gly215Ser). 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: 956516). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Prevention |
RCV003414027 | SCV004106567 | uncertain significance | ADAR-related condition | 2023-07-16 | criteria provided, single submitter | clinical testing | The ADAR c.643G>A variant is predicted to result in the amino acid substitution p.Gly215Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-154574475-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |