Submissions for variant NM_001182.5(ALDH7A1):c.796C>T (p.Arg266Ter)

gnomAD frequency: 0.00001  dbSNP: rs1270423610

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000553088	SCV000640329	pathogenic	Pyridoxine-dependent epilepsy	2023-10-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg266*) in the ALDH7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDH7A1 are known to be pathogenic (PMID: 16491085, 20554659). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with pyridoxine-dependent epilepsy (PMID: 19128417, 20554659). This variant is also known as c.712C>T (p.R238X). ClinVar contains an entry for this variant (Variation ID: 465333). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000760371	SCV000890234	pathogenic	not provided	2020-07-28	criteria provided, single submitter	clinical testing	Observed multiple times with a pathogenic variant in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in some cases ([described as R238X due to the use of alternative nomenclature]; Mathis et al., 2016; Xue et al., 2015; Oesch et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 29401530, 29875223, 19128417, 27342130, 26555630, 31737911, 20554659, 30043187)
CeGaT Center for Human Genetics Tuebingen	RCV000760371	SCV001245729	pathogenic	not provided	2017-01-01	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252160	SCV002523016	pathogenic	See cases	2021-02-19	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1, PS4, PM2, PM3
Revvity Omics, Revvity	RCV000553088	SCV003814934	pathogenic	Pyridoxine-dependent epilepsy	2022-03-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000553088	SCV004049234	pathogenic	Pyridoxine-dependent epilepsy	2023-04-11	criteria provided, single submitter	clinical testing