ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.3414+3A>T

gnomAD frequency: 0.00001  dbSNP: rs892742196
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002264936 SCV000520144 uncertain significance not provided 2022-07-11 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Labcorp Genetics (formerly Invitae), Labcorp RCV000529294 SCV000653691 pathogenic Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-08-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 381082). This variant has been observed in individuals with clinical features of autosomal recessive congenital myopathy (Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change falls in intron 26 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.
All of Us Research Program, National Institutes of Health RCV003996060 SCV004823980 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-12-18 criteria provided, single submitter clinical testing This variant causes an A to T nucleotide substitution at the +3 position of intron 26 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 autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar variation ID: 381082). This variant has been identified in 3/282872 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.
PreventionGenetics, part of Exact Sciences RCV003897864 SCV004709877 uncertain significance CACNA1S-related disorder 2024-05-26 no assertion criteria provided clinical testing The CACNA1S c.3414+3A>T variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0056% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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