ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5414_5417del (p.Thr1805fs)

dbSNP: rs1060501127
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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 RCV003654363 SCV000545016 pathogenic not provided 2025-01-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1806Serfs*27) in the SCN5A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 211 amino acid(s) of the SCN5A protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with atrioventricular block (PMID: 22899775). ClinVar contains an entry for this variant (Variation ID: 406415). This variant disrupts a region of the SCN5A protein in which other variant(s) (p.Glu1823Hisfs*10) have been determined to be pathogenic (PMID: 17897635, 18361072). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002348296 SCV002651564 likely pathogenic Cardiovascular phenotype 2019-09-12 criteria provided, single submitter clinical testing The c.5417_5420delCTCA variant, located in coding exon 27 of the SCN5A gene, results from a deletion of 4 nucleotides at nucleotide positions 5417 to 5420, causing a translational frameshift with a predicted alternate stop codon (p.T1806Sfs*27). This alteration has been reported in a subject with atrioventricular block and her similarly affected father (Baruteau AE et al. Circulation, 2012 Sep;126:1469-77). Frameshifts are typically deleterious in nature. Although this frameshift occurs at the 3' terminus of SCN5A and is not expected to trigger nonsense-mediated mRNA decay, it alters more than 10% of the protein. Based on the available evidence to date, this variant is likely to be pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002496750 SCV002810902 pathogenic Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2022-02-07 criteria provided, single submitter clinical testing

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