Submissions for variant NM_000069.3(CACNA1S):c.398+3G>A

gnomAD frequency: 0.00005  dbSNP: rs764710968

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000397402	SCV000353172	uncertain significance	Hypokalemic periodic paralysis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307110	SCV000353173	uncertain significance	Malignant hyperthermia of anesthesia	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000651213	SCV000773064	uncertain significance	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2022-08-15	criteria provided, single submitter	clinical testing	This sequence change falls in intron 3 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 (rs764710968, gnomAD 0.01%). 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: 294779). 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.
GeneDx	RCV000835462	SCV000977255	likely benign	not provided	2020-12-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000835462	SCV001150576	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	CACNA1S: PM2, BP4
Color Diagnostics, LLC DBA Color Health	RCV003517183	SCV004360413	uncertain significance	Malignant hyperthermia, susceptibility to, 5	2023-05-09	criteria provided, single submitter	clinical testing	This variant causes a G to A nucleotide substitution at the +3 position of intron 3 of the CACNA1S gene. 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 12/251482 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.