ClinVar Miner

Submissions for variant NM_174934.4(SCN4B):c.644_648del (p.Leu215fs)

dbSNP: rs778693616
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627664 SCV000748664 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN4B gene. The c.644_648delTGCC variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.644_648delTGCC variant causes a shift in reading frame starting at codon leucine 215, changing it to a tryptophan, and creating a premature stop codon at position 19 of the new reading frame, denoted p.Leu215TrpfsX19. However, this variant results in the last 14 amino acids being replaced with 18 incorrect amino acids and is not expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Finally, only one other frameshift variant in the SCN4B gene has been reported in Human Gene Mutation Database in association with SCN4B-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Ambry Genetics RCV004985020 SCV005500126 uncertain significance Cardiovascular phenotype 2024-12-04 criteria provided, single submitter clinical testing The c.644_648delTGCCT variant, located in coding exon 5 of the SCN4B gene, results from a deletion of 5 nucleotides at nucleotide positions 644 to 648, causing a translational frameshift with a predicted alternate stop codon (p.L215Wfs*19). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, the evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.

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