ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.393-5C>T

dbSNP: rs368678204
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000713141 SCV000681210 uncertain significance not provided 2022-12-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies are contradictory as to whether this variant significantly affects splicing (Frisso et al., 2016; O'Neill et al., 2022); Nucleotide substitution has no predicted effect on splicing and is not conserved across species; This variant is associated with the following publications: (PMID: 36197721, 27834932, 29998127)
Athena Diagnostics RCV000713141 SCV000843718 uncertain significance not provided 2017-12-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001841487 SCV000905089 likely benign Cardiac arrhythmia 2018-10-18 criteria provided, single submitter clinical testing
Invitae RCV000713141 SCV002439923 likely benign not provided 2023-09-05 criteria provided, single submitter clinical testing
Roden Lab, Vanderbilt University Medical Center RCV002298693 SCV002588731 likely benign Brugada syndrome 1 2022-10-05 criteria provided, single submitter research The SCN5A variant c.393-5C>T was observed in 1 case of Brugada Syndrome and is absent from large population databases (PMID: 32893267). The variant is not predicted to alter RNA splicing. The variant is associated with a non-canonical AT-AC splice junction. Functional studies in iPSC-CMs showed no determinental effect on splicing. These findings support a Likely Benign classification of this variant.
Ambry Genetics RCV002377201 SCV002626120 uncertain significance Cardiovascular phenotype 2022-06-14 criteria provided, single submitter clinical testing The c.393-5C>T intronic variant results from a C to T substitution 5 nucleotides upstream from coding exon 3 in the SCN5A gene. This nucleotide position is not well conserved in available vertebrate species. This alteration is located within a U12-type intron and in silico tools are not reliable predictors of splice sites in this type of intron. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001841487 SCV004815799 likely benign Cardiac arrhythmia 2024-01-11 criteria provided, single submitter clinical testing

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