Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003557744 | SCV004294196 | pathogenic | not provided | 2023-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 160 of the AAAS protein (p.His160Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with triple A syndrome (PMID: 11159947, 20499090, 21445602). 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 expected to disrupt AAAS protein function. Experimental studies have shown that this missense change affects AAAS function (PMID: 15666842, 16609705). For these reasons, this variant has been classified as Pathogenic. |