Submissions for variant NM_000702.4(ATP1A2):c.1097G>C (p.Gly366Ala)

dbSNP: rs1057518514

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412726	SCV000492241	uncertain significance	not specified	2016-12-01	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ATP1A2 gene. The G366A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G366A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species, and missense variants in nearby residues (V362E, T364M, T368K) have been reported in the Human Gene Mutation Database in association with hemiplegic migraine (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the G366A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
OMIM	RCV001777160	SCV002014589	pathogenic	Developmental and epileptic encephalopathy 98	2021-11-10	no assertion criteria provided	literature only