Submissions for variant NM_000069.3(CACNA1S):c.2593C>T (p.Arg865Cys)

gnomAD frequency: 0.00016  dbSNP: rs201205904

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000800242	SCV000939942	benign	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2023-11-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002495065	SCV002781681	uncertain significance	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1	2022-04-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003489884	SCV004234912	uncertain significance	not provided	2023-08-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003517269	SCV004360365	uncertain significance	Malignant hyperthermia, susceptibility to, 5	2022-11-06	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 865 of the CACNA1S protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has been identified in 27/282788 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.