ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.494G>C (p.Gly165Ala) (rs375491094)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724449 SCV000231000 uncertain significance not provided 2015-01-07 criteria provided, single submitter clinical testing
GeneDx RCV000724449 SCV000240329 uncertain significance not provided 2017-11-27 criteria provided, single submitter clinical testing p.Gly165Ala (G165A) (GGA>GCA): c.494 G>C in exon 5 of the ALDH7A1 gene (NM_001182.4) The G165A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different amino acid substitution at the same position (G165V) has been reported in the Human Gene Mutation Database in association with folinic-acid responsive seizures (Stenson et al., 2014). The 1000 Genomes Database reports G165A was observed in 1/172 (0.6%) alleles from individuals of Bengali ancestry; however, it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. However, the G165A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. 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.

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