Submissions for variant NM_000069.3(CACNA1S):c.1817G>A (p.Ser606Asn)

gnomAD frequency: 0.00873  dbSNP: rs142356235

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000349341	SCV000353085	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.
GeneDx	RCV000248889	SCV000521173	benign	not specified	2016-05-18	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083987	SCV000653650	benign	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711138	SCV000841466	benign	not provided	2018-05-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000711138	SCV002047948	benign	not provided	2023-08-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000711138	SCV002544351	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	CACNA1S: BS1, BS2
Genome-Nilou Lab	RCV003454730	SCV004178991	likely benign	Malignant hyperthermia, susceptibility to, 5	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003454731	SCV004178993	likely benign	Thyrotoxic periodic paralysis, susceptibility to, 1	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003458364	SCV004178994	likely benign	Congenital myopathy 18	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000349341	SCV004178995	likely benign	Hypokalemic periodic paralysis, type 1	2023-04-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003454730	SCV004360379	likely benign	Malignant hyperthermia, susceptibility to, 5	2018-03-05	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003454730	SCV004830120	likely benign	Malignant hyperthermia, susceptibility to, 5	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000711138	SCV005261074	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003891827	SCV000301805	benign	CACNA1S-related disorder	2020-03-30	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).