ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.553G>A (p.Val185Ile) (rs61757685)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186726 SCV000240293 uncertain significance not provided 2018-07-05 criteria provided, single submitter clinical testing The V185I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V185I variant is observed in 26/126,700 (0.02%) alleles from individuals of European background (Lek et al., 2016). The V185I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000702625 SCV000831485 uncertain significance Pyridoxine-dependent epilepsy 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 185 of the ALDH7A1 protein (p.Val185Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs61757685, ExAC 0.02%). This variant has not been reported in the literature in individuals with ALDH7A1-related disease. ClinVar contains an entry for this variant (Variation ID: 204830). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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