Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
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 | likely benign | Pyridoxine-dependent epilepsy | 2023-12-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002321750 | SCV002607787 | uncertain significance | Inborn genetic diseases | 2018-06-12 | criteria provided, single submitter | clinical testing | The c.31_33delCACinsGAG variant, located in coding exon 1 of the ALDH7A1 gene, results from an in-frame deletion of CAC and insertion of GAG at nucleotide positions 31 to 33. This results in the substitution of the histidine residue for a glutamic acid residue at codon 11, an amino acid with highly similar properties. Based on data from gnomAD, this alteration was deposited as two separate missense substitutions (c.31C>G; c.33C>G) each with an overall frequency of approximately 0.01% (21/184172; 20/183384) total alleles studied. The highest observed frequency for each was approximately 0.07% (19/25066; 18/25014) of Latino alleles. This amino acid position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |