Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000417460 | SCV000530343 | uncertain significance | not provided | 2018-03-16 | criteria provided, single submitter | clinical testing | The T426A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense variant at the same position (T426P) has been reported previously (using alternative nomenclature of T398P) in siblings with pyridoxine-dependent epilepsy who have a second ALDH7A1 variant on the other chromosome (Mills et al., 2010). The T426A variant is observed in 13/24024 (0.05%) alleles from individuals of African background, in large population cohorts (Lek et al., 2016). The T426A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with ALDH7A1-related disorders (Stenson et al., 2014). However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000814956 | SCV000955395 | likely benign | Pyridoxine-dependent epilepsy | 2023-11-18 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000814956 | SCV001529631 | uncertain significance | Pyridoxine-dependent epilepsy | 2018-07-30 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002374690 | SCV002684862 | uncertain significance | Inborn genetic diseases | 2017-10-27 | criteria provided, single submitter | clinical testing | The p.T426A variant (also known as c.1276A>G), located in coding exon 14 of the ALDH7A1 gene, results from an A to G substitution at nucleotide position 1276. The threonine at codon 426 is replaced by alanine, an amino acid with similar properties. In one study, a different alteration located at the same position, p.T426P (which is referred to as p.T398P in the paper), was detected in three siblings with pyridoxine-dependent epilepsy (PDE) who also carried ALDH7A1 p.A129P on their opposite chromosome(s) (in trans) (Mills PB et al. Brain, 2010 Jul;133:2148-59). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |