ClinVar Miner

Submissions for variant NM_001111.5(ADAR):c.2275G>A (p.Val759Ile)

gnomAD frequency: 0.00006  dbSNP: rs145849344
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000809038 SCV000949174 uncertain significance Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 759 of the ADAR protein (p.Val759Ile). This variant is present in population databases (rs145849344, gnomAD 0.02%). 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: 653292). 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 with a negative predictive value of 80%. 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.
GeneDx RCV001571860 SCV001796404 uncertain significance not provided 2023-01-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Revvity Omics, Revvity RCV001571860 SCV003824983 uncertain significance not provided 2020-11-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003338815 SCV004050349 uncertain significance Aicardi-Goutieres syndrome 6 2023-04-11 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003892728 SCV004708511 uncertain significance ADAR-related condition 2023-12-04 criteria provided, single submitter clinical testing The ADAR c.2275G>A variant is predicted to result in the amino acid substitution p.Val759Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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