ClinVar Miner

Submissions for variant NM_001080.3(ALDH5A1):c.667T>C (p.Cys223Arg)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Elsea Laboratory, Baylor College of Medicine RCV002510251 SCV002819994 likely pathogenic Succinate-semialdehyde dehydrogenase deficiency 2021-03-08 criteria provided, single submitter curation
Labcorp Genetics (formerly Invitae), Labcorp RCV002510251 SCV003439366 pathogenic Succinate-semialdehyde dehydrogenase deficiency 2022-05-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ALDH5A1 function (PMID: 32402538). 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 ALDH5A1 protein function. This missense change has been observed in individual(s) with succinic semialdehyde dehydrogenase deficiency (PMID: 19484191, 32402538). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 223 of the ALDH5A1 protein (p.Cys223Arg).
Ambry Genetics RCV002571583 SCV003548880 likely pathogenic Inborn genetic diseases 2020-12-07 criteria provided, single submitter clinical testing The c.667T>C (p.C223R) alteration is located in exon 4 (coding exon 4) of the ALDH5A1 gene. This alteration results from a T to C substitution at nucleotide position 667, causing the cysteine (C) at amino acid position 223 to be replaced by an arginine (R). Based on the available evidence, this alteration is classified as likely pathogenic.

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