ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.3256C>T (p.Arg1086Cys) (rs80338782)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540523 SCV000653689 uncertain significance Hypokalemic periodic paralysis 1; Malignant hyperthermia, susceptibility to, 5 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1086 of the CACNA1S protein (p.Arg1086Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs80338782, ExAC 0.01%). This variant has been observed in a family affected with malignant hyperthermia (PMID: 10590402). ClinVar contains an entry for this variant (Variation ID: 21035). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg1086 amino acid residue in CACNA1S. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9199552, 11260227, 12411788, 20431982). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 Praxis fuer Humangenetik Tuebingen RCV000761690 SCV000891869 uncertain significance not provided 2019-09-01 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148445 SCV000190144 uncertain significance Hypokalemic periodic paralysis 2014-06-01 no assertion criteria provided research

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