ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.1066C>G (p.Gln356Glu) (rs138675705)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725331 SCV000336102 uncertain significance not provided 2015-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000725331 SCV000533079 uncertain significance not provided 2018-11-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALDH7A1 gene. The Q356E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The Q356E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species/conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is 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 RCV000815892 SCV000956370 uncertain significance Pyridoxine-dependent epilepsy 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 356 of the ALDH7A1 protein (p.Gln356Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs138675705, 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: 283788). 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 C25"). 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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