Submissions for variant NM_000335.5(SCN5A):c.274-5C>G

dbSNP: rs773669619

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV001591695	SCV001815729	uncertain significance	not provided	2020-11-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001591695	SCV001991529	uncertain significance	not provided	2019-03-04	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001591695	SCV002218712	uncertain significance	not provided	2022-12-24	criteria provided, single submitter	clinical testing	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. 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: 1213746). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is present in population databases (rs773669619, gnomAD 0.02%). This sequence change falls in intron 2 of the SCN5A gene. It does not directly change the encoded amino acid sequence of the SCN5A protein.
Ambry Genetics	RCV002440821	SCV002748945	uncertain significance	Cardiovascular phenotype	2019-05-31	criteria provided, single submitter	clinical testing	The c.274-5C>G intronic variant results from a C to G substitution 5 nucleotides upstream from coding exon 2 in the SCN5A gene. This nucleotide position is not well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice acceptor site, but is predicted to weaken (but not abolish) the efficiency of the native splice acceptor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002488418	SCV002788029	uncertain significance	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	2022-03-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004008943	SCV004840283	uncertain significance	Cardiac arrhythmia	2023-12-18	criteria provided, single submitter	clinical testing	This variant is located in intron 2 of the SCN5A gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 4/249304 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.