ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.1193G>T (p.Gly398Val)

dbSNP: rs864622557
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205037 SCV000261113 pathogenic Pyridoxine-dependent epilepsy 2016-01-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 398 of the ALDH7A1 protein (p.Gly398Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. This variant is associated with elevated alpha-AASA in urine in this patient, pyridoxine responsive seizures, and has been confirmed in trans with another pathogenic variant in ALDH7A1 through parental testing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. A different missense substitution at this codon (p.Gly398Arg) is reported to be deleterious (PMID: 22529283). This indicates that the glycine residue is important for ALDH7A1 protein function. For these reasons, this variant has been classified as Pathogenic.

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