ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.1882G>A (p.Val628Met)

dbSNP: rs1553245659
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521836 SCV000617441 pathogenic not provided 2023-01-13 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (Vanmolkot et al., 2006; Schack et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23561701, 16538223, 23202128, 27445835, 18184292, 18846413, 22117059)
CeGaT Center for Human Genetics Tuebingen RCV000521836 SCV001249778 pathogenic not provided 2023-03-01 criteria provided, single submitter clinical testing ATP1A2: PP1:Strong, PM1, PM2, PS4:Moderate, PP3, PS3:Supporting
Invitae RCV001385317 SCV001585132 pathogenic Familial hemiplegic migraine 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 628 of the ATP1A2 protein (p.Val628Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial hemiplegic migraine (PMID: 16538223). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449380). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP1A2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 16538223). For these reasons, this variant has been classified as Pathogenic.

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