ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.1267C>T (p.Arg423Cys) (rs370654268)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000593090 SCV000705845 uncertain significance not provided 2017-02-06 criteria provided, single submitter clinical testing
Invitae RCV000593090 SCV001575991 likely pathogenic not provided 2020-08-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 423 of the ALDH3A2 protein (p.Arg423Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs370654268, ExAC 0.01%). This variant has not been reported in the literature in individuals with ALDH3A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 500063). 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. This variant disrupts the p.Arg423 amino acid residue in ALDH3A2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10577908, 15241804). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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