Submissions for variant NM_000335.5(SCN5A):c.998+5G>A

gnomAD frequency: 0.00019  dbSNP: rs187531872

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151802	SCV000200265	uncertain significance	not specified	2019-02-07	criteria provided, single submitter	clinical testing	The 998+5G>A variant in SCN5A has not been reported in individuals with cardiomyopathy, but it has been identified in 1/8366 of European American chromosomes by the NHLBI Exome Sequencing Project and in 0.5% (1/186) of Finnish chromosomes by the 1000 Genomes Project (http://evs.gs.washington.edu/EVS/;dbSNP rs187531872). This variant is located in the 5' splice region. Computational tools suggest a possible impact to splicing. However, this information is not predictive enough to determine pathogenicity. Additional information is needed to fully assess the clinical significance of the 998+5G>A variant. 998+5G>A intron 8 of SCN5A (rs187531872; allele frequency = 1/8366). This variant has been seen by several clinical labs in ClinVar (uncertain significance), and affects splice in silico. This variant has been reported in an individual affected with long QT syndrome (PMID: 23631430).
Blueprint Genetics	RCV000157496	SCV000207241	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2015-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252811	SCV000320385	likely benign	Cardiovascular phenotype	2021-07-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV003764926	SCV000760233	likely benign	not provided	2023-12-22	criteria provided, single submitter	clinical testing
Klaassen Lab, Charite University Medicine Berlin	RCV000853149	SCV000995862	uncertain significance	Primary dilated cardiomyopathy	2019-07-03	criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV001842475	SCV001356063	likely benign	Cardiac arrhythmia	2023-03-15	criteria provided, single submitter	clinical testing