Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001958936 | SCV002240232 | pathogenic | not provided | 2023-05-15 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects ALDH3A2 function (PMID: 10577908). For these reasons, this variant has been classified as Pathogenic. 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 ALDH3A2 protein function. ClinVar contains an entry for this variant (Variation ID: 1459314). This missense change has been observed in individual(s) with ALDH3A2-related conditions (PMID: 10577908, 15241804). This variant is present in population databases (rs768290318, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 423 of the ALDH3A2 protein (p.Arg423His). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230721 | SCV003928954 | likely pathogenic | Sjögren-Larsson syndrome | 2023-04-05 | criteria provided, single submitter | clinical testing | Variant summary: ALDH3A2 c.1268G>A (p.Arg423His) results in a non-conservative amino acid change to a highly conserved residue (HGMD) in the dimerisation interface (Keller_2014) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251464 control chromosomes. c.1268G>A has been reported in the literature in individuals affected with Sjogren-Larsson Syndrome (Rizzo_1999, Carney_2004), and one of these was reported as compound heterozygous with a pathogenic variant. These data indicate that the variant is likely associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, resulting in 1% of normal FALDH enzymatic activity (Rizzo_1999). One submitter has provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV003230721 | SCV005644806 | likely pathogenic | Sjögren-Larsson syndrome | 2024-02-17 | criteria provided, single submitter | clinical testing |