Gene: SCN5A ×
Source: ALL
Variant Gene Risk Allele Score vda Association Type Original DB Sentence supporting the association PMID PMID Year
dbSNP: rs137854600
rs137854600
SCN5A
0.840 GeneticVariation BEFREE These findings explain the unusual drug sensitivity of R1623Q and provide a general and unanticipated mechanism for understanding how Na channel-blocking agents may suppress the pathologic, sustained Na current induced by LQT3 mutations. 10772658

2000
dbSNP: rs137854600
rs137854600
SCN5A
0.840 GeneticVariation BEFREE Here we characterized a de novo missense mutation (R1623Q, S4 segment of domain 4) identified in an infant Japanese girl with a severe form of LQT3. 9506831

1998
dbSNP: rs137854600
rs137854600
SCN5A
0.840 GeneticVariation BEFREE The presence of two slowly inactivating mutants of the cardiac sodium channel (hNa(V)1.5), R1623Q and R1626P, associate with sporadic Long-QT3 (LQT3) syndrome, and may contribute to ventricular tachyarrhythmias and/or lethal ventricular disturbances. 20090423

2010
dbSNP: rs137854600
rs137854600
SCN5A
0.840 GeneticVariation BEFREE The R1623Q mutation produces inactivation gating defects that differ mechanistically from those caused by LQT3 mutations. 9495298

1998
dbSNP: rs137854601
rs137854601
SCN5A
0.820 GeneticVariation BEFREE E1784K is the most common mixed syndrome SCN5a mutation underpinning both Brugada syndrome type 1 (BrS1) and Long-QT syndrome type 3 (LQT3). 29483621

2018
dbSNP: rs137854601
rs137854601
SCN5A
0.820 GeneticVariation BEFREE Heterologously expressed E1784K channels showed a 15.0-mV negative shift in the voltage dependence of Na channel inactivation and a 7.5-fold increase in flecainide affinity for resting-state channels, properties also seen with other LQT3 mutations associated with a mixed clinical phenotype. 18451998

2008
dbSNP: rs137854614
rs137854614
SCN5A
0.810 GeneticVariation BEFREE Interestingly another LQT-3 mutant (Y1795C) shows no change in flecainide sensitivity, suggesting that although drug effects of SCN5A mutations cross disease boundaries, clinical management with flecainide will be beneficial to patients in a mutation-specific manner. 12814325

2003
dbSNP: rs199473283
rs199473283
SCN5A
0.810 GeneticVariation BEFREE The presence of two slowly inactivating mutants of the cardiac sodium channel (hNa(V)1.5), R1623Q and R1626P, associate with sporadic Long-QT3 (LQT3) syndrome, and may contribute to ventricular tachyarrhythmias and/or lethal ventricular disturbances. 20090423

2010
dbSNP: rs199473311
rs199473311
SCN5A
0.810 GeneticVariation BEFREE Here we describe a novel LQT-3 mutation I1768V (I1768V) located in the sixth transmembrane spanning segment of domain IV. 12209021

2002
dbSNP: rs199473603
rs199473603
SCN5A
0.810 GeneticVariation BEFREE Furthermore, these properties were absent in Na channels harboring the T1304M mutation, which is associated with LQT3 without a mixed clinical phenotype. 18451998

2008
dbSNP: rs199473317
rs199473317
SCN5A
0.730 GeneticVariation BEFREE Ranolazine blocks I<sub>NaL</sub> in experimental models of LQT3 harboring the SCN5A-D1790G mutation and shortened the QT interval of LQT3 patients. 27733495

2016
dbSNP: rs199473317
rs199473317
SCN5A
0.730 GeneticVariation BEFREE D1790G (DG), an LQT-3 mutation of the C-terminal region of the Na(+) channel alpha-subunit, alters steady-state inactivation of expressed channels but does not promote sustained Na(+) channel activity. 10952963

2000
dbSNP: rs199473317
rs199473317
SCN5A
0.730 GeneticVariation BEFREE The objective of the current study was to evaluate the long-term safety and efficacy of flecainide therapy in patients with LQT3 who carry the D1790G SCN5A mutation. 28339995

2018
dbSNP: rs199473133
rs199473133
SCN5A
0.710 GeneticVariation BEFREE A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating. 12673799

2003
dbSNP: rs199473225
rs199473225
SCN5A
0.710 GeneticVariation BEFREE While A647D mitigates the lethal LQT3 phenotype seen with P1332L, it also reduces mexilitine sensitivity and decreases INa density. 29791480

2018
dbSNP: rs199473631
rs199473631
SCN5A
0.710 GeneticVariation BEFREE Dermal fibroblasts obtained from a patient with LQT3 harboring a SCN5A mutation (c.5287G>A; p.V1763M) were reprogrammed to hiPSCs via repeated transfection of mRNA encoding OCT-4, SOX-2, KLF-4, C-MYC and LIN-28. hiPSC-derived cardiomyocytes (hiPSC-CMs) were obtained via cardiac differentiation. hiPSC-CMs derived from the patient's healthy sister were used as a control. 23998552

2013
dbSNP: rs79299226
rs79299226
SCN5A
0.710 GeneticVariation BEFREE Although L1825P generates late sodium current typical of SCN5A-linked long-QT syndrome (LQT3) in vitro, the patient reported had a normal QT interval before administration of the drug. 16301357

2005
dbSNP: rs137854615
rs137854615
SCN5A
0.010 GeneticVariation BEFREE Channels associated with LQT-3 (D1790G) and BrS (Y1795H) both show more sensitivity to flecainide than wild-type (WT) channels, while lidocaine sensitivity is unchanged. 12814325

2003
dbSNP: rs185638763
rs185638763
SCN5A
0.010 GeneticVariation BEFREE While A647D mitigates the lethal LQT3 phenotype seen with P1332L, it also reduces mexilitine sensitivity and decreases INa density. 29791480

2018
dbSNP: rs199473316
rs199473316
SCN5A
0.010 GeneticVariation BEFREE Four variants (F1293S, R1512W, and V1951L cited previously as BrS1-causing mutations and S1787N previously published as a possible LQT3-causing mutation) were identified in this healthy cohort. 15851227

2004
dbSNP: rs41310765
rs41310765
SCN5A
0.010 GeneticVariation BEFREE This study shows LQT3 features associated with an A1180V cardiac sodium channel mutation, expanding the spectrum of phenotypes resulting from this mutation in which biophysical study has shown a persistent late Na(+) current. 23963187

2014
dbSNP: rs137854600
rs137854600
SCN5A
T 0.840 CausalMutation CLINVAR

dbSNP: rs137854601
rs137854601
SCN5A
T 0.820 CausalMutation CLINVAR The implications of familial incidental findings from exome sequencing: the NIH Undiagnosed Diseases Program experience. 24784157

2014
dbSNP: rs137854601
rs137854601
SCN5A
T 0.820 CausalMutation CLINVAR Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome. 21321465

2011
dbSNP: rs137854601
rs137854601
SCN5A
T 0.820 CausalMutation CLINVAR Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. 10377081

1999