ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.2936C>T (p.Pro979Leu)

dbSNP: rs121918615
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529838 SCV000632374 pathogenic Familial hemiplegic migraine 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 979 of the ATP1A2 protein (p.Pro979Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with familial and sporadic hemiplegic migraine (PMID: 15159495, 23821026, 27790126). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12925). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATP1A2 protein function. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 19372756). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001560539 SCV001782970 pathogenic not provided 2019-10-08 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, with P979L resulting in an unstable protein at physiological temperature comparing with wild type (Tavraz et al., 2009); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 16437583, 19673908, 28479855, 15907261, 18184292, 27790126, 23821026, 19372756, 15159495)
Institute of Human Genetics, University of Leipzig Medical Center RCV000013788 SCV003921044 pathogenic Migraine, familial hemiplegic, 2 2023-02-16 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PS3, PS4_MOD, PM2_SUP, PP2, PP3, PP4
OMIM RCV000013788 SCV000034035 pathogenic Migraine, familial hemiplegic, 2 2004-05-25 no assertion criteria provided literature only
GeneReviews RCV000529838 SCV001748972 not provided Familial hemiplegic migraine no assertion provided literature only Severe phenotype reported
GenomeConnect - Brain Gene Registry RCV003313029 SCV004012822 not provided Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic, 2 no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 06-11-2018 by Lab Children's National Medical Center. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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