Submissions for variant NM_000069.3(CACNA1S):c.1827+6C>T

gnomAD frequency: 0.00001  dbSNP: rs202244301

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000689838	SCV000817507	uncertain significance	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change falls in intron 12 of the CACNA1S gene. It does not directly change the encoded amino acid sequence of the CACNA1S protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs202244301, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 569254). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Fulgent Genetics, Fulgent Genetics	RCV002485628	SCV002775110	uncertain significance	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1	2022-01-17	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446349	SCV004173263	uncertain significance	Malignant hyperthermia, susceptibility to, 5	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446350	SCV004173265	uncertain significance	Thyrotoxic periodic paralysis, susceptibility to, 1	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446351	SCV004173266	uncertain significance	Congenital myopathy 18	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446348	SCV004173267	uncertain significance	Hypokalemic periodic paralysis, type 1	2023-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003907948	SCV004721532	likely benign	CACNA1S-related condition	2020-09-30	criteria provided, single submitter	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).