Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186723 | SCV000240290 | uncertain significance | not provided | 2014-02-14 | criteria provided, single submitter | clinical testing | p.Arg122Pro (CGG>CCG): c.365 G>C in exon 4 of the ALDH7A1 gene (NM_001182.4). A variant of unknown significance has been identified in the ALDH7A1 gene. The Arg122Pro variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Arg122Pro 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 propertiesThis substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |
Invitae | RCV001043918 | SCV001207687 | likely pathogenic | Pyridoxine-dependent epilepsy | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 122 of the ALDH7A1 protein (p.Arg122Pro). This variant is present in population databases (rs796052256, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ALDH7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 204827). 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%. This variant disrupts the p.Arg122 amino acid residue in ALDH7A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Ambry Genetics | RCV002516977 | SCV003562834 | uncertain significance | Inborn genetic diseases | 2021-09-21 | criteria provided, single submitter | clinical testing | The c.365G>C (p.R122P) alteration is located in exon 4 (coding exon 4) of the ALDH7A1 gene. This alteration results from a G to C substitution at nucleotide position 365, causing the arginine (R) at amino acid position 122 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |