Submissions for variant NM_001182.5(ALDH7A1):c.1483G>A (p.Ala495Thr)

dbSNP: rs1749930972

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003120690	SCV003785599	pathogenic	Pyridoxine-dependent epilepsy	2024-06-21	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 495 of the ALDH7A1 protein (p.Ala495Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pyridoxine-dependent epilepsy (PMID: 23683770, 24789515). This variant is also known as c.1399G>A (p.A467T). ClinVar contains an entry for this variant (Variation ID: 1328029). 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%. For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001794978	SCV002034085	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001794978	SCV002037304	likely pathogenic	not provided		no assertion criteria provided	clinical testing