ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.483-3C>G

dbSNP: rs759754258
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000792612 SCV000931918 uncertain significance Hyperkalemic periodic paralysis 2024-10-17 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the SCN4A gene. It does not directly change the encoded amino acid sequence of the SCN4A protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. ClinVar contains an entry for this variant (Variation ID: 639733). 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. 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.
Illumina Laboratory Services, Illumina RCV001796220 SCV002034812 uncertain significance SCN4A-related myopathy, autosomal recessive 2021-07-01 criteria provided, single submitter clinical testing The SCN4A c.483-3C>G variant is a splice region variant. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The variant is reported at a frequency of 0.000026 in the Total population of the Genome Aggregation Database (version 3.1.1) in a region of good sequence coverage. In silico tools predict this variant may result in a new cryptic splice but this prediction has not been confirmed experimentally. Based on the limited evidence, the c.483-3C>G variant is classified as a variant of uncertain significance for SCN4A-related myopathy.
Fulgent Genetics, Fulgent Genetics RCV005004423 SCV002785396 uncertain significance Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal 2024-04-26 criteria provided, single submitter clinical testing

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