Submissions for variant NM_000069.3(CACNA1S):c.1881C>T (p.Tyr627=)

gnomAD frequency: 0.00009  dbSNP: rs145689664

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385096	SCV000353080	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	RCV000892976	SCV001036887	likely benign	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2024-11-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003454898	SCV004178976	benign	Malignant hyperthermia, susceptibility to, 5	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003454899	SCV004178977	benign	Thyrotoxic periodic paralysis, susceptibility to, 1	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003458410	SCV004178978	benign	Congenital myopathy 18	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000385096	SCV004178979	benign	Hypokalemic periodic paralysis, type 1	2023-04-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003454898	SCV004827720	likely benign	Malignant hyperthermia, susceptibility to, 5	2024-02-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930220	SCV004750538	likely benign	CACNA1S-related disorder	2019-07-01	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).