ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.7C>T (p.Arg3Cys)

gnomAD frequency: 0.00001  dbSNP: rs796052265
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186751 SCV000240318 uncertain significance not provided 2013-04-24 criteria provided, single submitter clinical testing p.Arg3Cys (CGC>TGC): c.7 C>T in exon 1 of the ALDH7A1 gene (NM_001182.3). The Arg3Cys missense change in the ALDH7A1 gene 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 2,200 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 amino acid substitution is non-conservative as a positively charged Arginine residue is replaced by an uncharged Cysteine residue and the gain of a Cysteine may affect disulfide bond formation in the ALDH7A1 protein. Arg3Cys alters a position that is conserved in mammals but not in related proteins and other missense mutations have not been reported in this region of the protein. In addition, in-silico algorithms are not consistent in their predictions of whether Arg3Cys is damaging to the structure/function of the protein. Therefore, based on the currently available information, it is unclear whether Arg3Cys is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV001852438 SCV002309276 uncertain significance Pyridoxine-dependent epilepsy 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 3 of the ALDH7A1 protein (p.Arg3Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. 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: 204853). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Genome-Nilou Lab RCV001852438 SCV004048590 uncertain significance Pyridoxine-dependent epilepsy 2023-04-11 criteria provided, single submitter clinical testing

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