Submissions for variant NM_001111.5(ADAR):c.1372G>A (p.Asp458Asn)

dbSNP: rs759763367

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001097510	SCV001253799	uncertain significance	Symmetrical dyschromatosis of extremities	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics	RCV002555997	SCV003672496	uncertain significance	Inborn genetic diseases	2022-12-28	criteria provided, single submitter	clinical testing	The c.1372G>A (p.D458N) alteration is located in exon 2 (coding exon 2) of the ADAR gene. This alteration results from a G to A substitution at nucleotide position 1372, causing the aspartic acid (D) at amino acid position 458 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV003339485	SCV004050371	uncertain significance	Aicardi-Goutieres syndrome 6	2023-04-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV005225229	SCV005867781	uncertain significance	Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6	2025-01-30	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 458 of the ADAR protein (p.Asp458Asn). This variant is not present in population databases (gnomAD no frequency). 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: 874511). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.