Submissions for variant NM_001605.2(AARS1):c.1222G>A (p.Gly408Arg) (rs369135192)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235471	SCV000293937	uncertain significance	not provided	2016-02-23	criteria provided, single submitter	clinical testing	The G408R 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 G480R 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. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with AARS-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV000999705	SCV001156491	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing