ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.914C>G (p.Ala305Gly) (rs141775154)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493795 SCV000582126 uncertain significance not provided 2017-05-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALDH7A1 gene. The A305G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A305G variant is observed in 6/10326 (0.06%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A305G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties and this substitution occurs at a position that is not conserved. However, 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 variant or a rare benign variant.
Invitae RCV000473337 SCV000551316 uncertain significance Pyridoxine-dependent epilepsy 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 305 of the ALDH7A1 protein (p.Ala305Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs141775154, ExAC 0.06%). This variant has not been reported in the literature in individuals with ALDH7A1-related disease. ClinVar contains an entry for this variant (Variation ID: 410541). Algorithms developed to predict the effect of missense changes on protein structure and function 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.

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