ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.31_33delinsGAG (p.His11Glu) (rs796052269)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186759 SCV000240326 uncertain significance not specified 2015-01-05 criteria provided, single submitter clinical testing c.31_33delCACinsGAG: p.His11Glu (H11E) in exon 1 of the ALDH7A1 gene (NM_001182.4). The normal sequence with the bases that are deleted in braces followed by the inserted bases in brackets is: CTGTGTGTG{CAC}[GAG] GCTG. The c.31_33delCACinsGAG variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.31_33delCACinsGAG variant results in an in-frame deletion of a single Histidine residue and the insertion of a single Glutamic acid residue, denoted p.His11Glu (H11E). The H11E 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, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000538073 SCV000640319 uncertain significance Pyridoxine-dependent epilepsy 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamic acid at codon 11 of the ALDH7A1 protein (p.His11Glu). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ALDH7A1-related disease. ClinVar contains an entry for this variant (Variation ID: 204861). 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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