Submissions for variant NM_000702.4(ATP1A2):c.2501G>A (p.Arg834Gln)

dbSNP: rs2101995864

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001385318	SCV001585133	pathogenic	Familial hemiplegic migraine	2023-01-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 18728015, 22117059, 24704353). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 834 of the ATP1A2 protein (p.Arg834Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with familial hemiplegic migraine (PMID: 16088919; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1072573). 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 disruptive.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV002468636	SCV002764795	pathogenic	Migraine, familial hemiplegic, 2	2020-12-21	criteria provided, single submitter	clinical testing