Submissions for variant NM_000069.3(CACNA1S):c.2439C>T (p.Ser813=)

gnomAD frequency: 0.00005  dbSNP: rs376863448

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000365113	SCV000353048	benign	Hypokalemic periodic paralysis, type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083984	SCV000653667	likely benign	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2025-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000601492	SCV000726960	likely benign	not specified	2018-01-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics	RCV000553748	SCV001143492	benign	not provided	2019-06-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003454896	SCV004177887	benign	Malignant hyperthermia, susceptibility to, 5	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003454897	SCV004177888	benign	Thyrotoxic periodic paralysis, susceptibility to, 1	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003458409	SCV004177889	benign	Congenital myopathy 18	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000365113	SCV004177890	benign	Hypokalemic periodic paralysis, type 1	2023-04-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003454896	SCV004823444	likely benign	Malignant hyperthermia, susceptibility to, 5	2023-12-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003982998	SCV004796101	likely benign	CACNA1S-related disorder	2019-04-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).