Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186754 | SCV000240321 | uncertain significance | not provided | 2018-09-21 | criteria provided, single submitter | clinical testing | p.Ser23Gly (AGC>GGC): c.67 A>G in exon 1 of the ALDH7A1 gene (NM_001182.4). The S23G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S23G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The S23G 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. 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. The variant is found in EPILEPSY panel(s). |
Labcorp Genetics |
RCV001307332 | SCV001496739 | uncertain significance | Pyridoxine-dependent epilepsy | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with glycine at codon 23 of the ALDH7A1 protein (p.Ser23Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). 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: 204856). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002513978 | SCV003697546 | uncertain significance | Inborn genetic diseases | 2022-06-17 | criteria provided, single submitter | clinical testing | The c.67A>G (p.S23G) alteration is located in exon 1 (coding exon 1) of the ALDH7A1 gene. This alteration results from a A to G substitution at nucleotide position 67, causing the serine (S) at amino acid position 23 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome- |
RCV001307332 | SCV004050431 | uncertain significance | Pyridoxine-dependent epilepsy | 2023-04-11 | criteria provided, single submitter | clinical testing |