ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.1151G>A (p.Gly384Glu)

gnomAD frequency: 0.00004  dbSNP: rs201737381
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002013044 SCV002294575 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 384 of the CACNA1S protein (p.Gly384Glu). This variant is present in population databases (rs201737381, gnomAD 0.002%). 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: 1499796). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV002492312 SCV002789693 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1 2022-05-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002642096 SCV003691921 uncertain significance Inborn genetic diseases 2021-09-15 criteria provided, single submitter clinical testing The c.1151G>A (p.G384E) alteration is located in exon 9 (coding exon 9) of the CACNA1S gene. This alteration results from a G to A substitution at nucleotide position 1151, causing the glycine (G) at amino acid position 384 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003453946 SCV004179171 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003453947 SCV004179172 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003458815 SCV004179173 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003453945 SCV004179174 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003453946 SCV004843024 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces glycine with glutamic acid at codon 384 of the CACNA1S protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). 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 3/279606 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.

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