Submissions for variant NM_000702.4(ATP1A2):c.589G>A (p.Val197Ile)

gnomAD frequency: 0.00002  dbSNP: rs540087535

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001363855	SCV001559984	uncertain significance	Familial hemiplegic migraine	2025-01-30	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 197 of the ATP1A2 protein (p.Val197Ile). This variant is present in population databases (rs540087535, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1055216). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATP1A2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV001796463	SCV004125072	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	ATP1A2: BP4
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001796463	SCV002034284	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001796463	SCV002035460	likely benign	not provided		no assertion criteria provided	clinical testing