ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.788C>T (p.Thr263Met)

dbSNP: rs777400961
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000710694 SCV000840979 pathogenic not provided 2018-07-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001868323 SCV002262761 likely pathogenic Familial hemiplegic migraine 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 263 of the ATP1A2 protein (p.Thr263Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant familial hemiplegic migraine (PMID: 16088919; Invitae). ClinVar contains an entry for this variant (Variation ID: 585463). 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: 18728015, 22117059). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV003128252 SCV003804693 likely pathogenic Migraine, familial hemiplegic, 2 2023-01-09 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PS3_MOD, PS4_MOD, PM1, PP1_MOD, PM2_SUP, PP3
GeneDx RCV000710694 SCV005201791 likely pathogenic not provided 2023-10-08 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on protein function (PMID: 22117059, 18728015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24096472, 22067897, 18728015, 16088919, 22117059)

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