Submissions for variant NM_000335.5(SCN5A):c.1045G>A (p.Asp349Asn)

gnomAD frequency: 0.00001  dbSNP: rs779687673

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000213192	SCV000272405	uncertain significance	not specified	2016-02-16	criteria provided, single submitter	clinical testing	The p.Asp349Asn variant in SCN5A has been identified in one Caucasian individual with Brugada syndrome and as a compound heterozygote in one individual with sic k sinus syndrome (Kodma 2013, Savastano 2013). It has been identified in 2/1156 4 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs779687673). Computational prediction tools and conservat ion analysis suggest that the p.Asp349Asn variant may not impact the protein, th ough this information is not predictive enough to rule out pathogenicity. In sum mary, the clinical significance of the p.Asp349Asn variant is uncertain.
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV000678960	SCV000805176	uncertain significance	Brugada syndrome 1	2018-05-15	criteria provided, single submitter	clinical testing
Invitae	RCV002223194	SCV001391686	likely pathogenic	not provided	2023-12-07	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 349 of the SCN5A protein (p.Asp349Asn). This variant is present in population databases (rs779687673, gnomAD 0.009%). This missense change has been observed in individuals with Brugada syndrome (PMID: 23200271, 24721456, 29709101, 31737537, 33221895, 36220970). ClinVar contains an entry for this variant (Variation ID: 229230). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 32533946) did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN5A function. Experimental studies have shown that this missense change affects SCN5A function (PMID: 32533946). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
AiLife Diagnostics, AiLife Diagnostics	RCV002223194	SCV002501488	uncertain significance	not provided	2021-06-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV002223194	SCV003821325	uncertain significance	not provided	2022-05-18	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV002223194	SCV004226073	uncertain significance	not provided	2022-05-20	criteria provided, single submitter	clinical testing	PS3_supporting, PS4_supporting
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001219733	SCV001571567	uncertain significance	Brugada syndrome	2020-08-14	no assertion criteria provided	clinical testing