ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.1004G>A (p.Arg335Gln)

gnomAD frequency: 0.00002  dbSNP: rs754449549
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186728 SCV000240295 pathogenic not provided 2021-12-30 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on enzyme activity (Coulter-Mackie et al., 2012); This variant is associated with the following publications: (PMID: 19128417, 30043187, 32956737, 27342130, Ambegaonkar2017[abstract], 17068770, 24942048, 22784480)
Invitae RCV000796632 SCV000936153 pathogenic Pyridoxine-dependent epilepsy 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 335 of the ALDH7A1 protein (p.Arg335Gln). This variant is present in population databases (rs754449549, gnomAD 0.007%). This missense change has been observed in individual(s) with pyridoxine-dependent epilepsy (PMID: 17068770; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.920G>A (p.Arg307Gln). ClinVar contains an entry for this variant (Variation ID: 204832). 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 ALDH7A1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ALDH7A1 function (PMID: 22784480). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000186728 SCV002497346 likely pathogenic not provided 2022-01-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000796632 SCV004048968 likely pathogenic Pyridoxine-dependent epilepsy 2023-04-11 criteria provided, single submitter clinical testing

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