SCN5A Variant c.692_693delCA

Summary of observed carriers, functional annotations, and structural context for SCN5A c.692_693delCA. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

38%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.692_693delCA has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
NA NA NA None 44 3

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
23538678 2013 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 12 0 3 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
23538678 2013

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near c.692_693delCA.
Neighbour residue Distance (Å) Observed variants
848 11 I848F
842 14
240 9 V240M,
231 0 c.692_693delCA,
131 13
193 9 W193R, W193R, W193X,
237 9
228 6 K228R,
138 8 M138I, M138I, M138I,
227 9 L227P,
171 15
137 11 I137V,
234 9 P234S,
142 11
197 12
229 6
196 13
852 15
224 14 L224F,
845 10 c.2533delG,
232 4 V232I, V232F,
244 14
133 14
191 14
134 10 N134S,
849 14
226 10 A226G, A226V,
241 13
235 9 c.703+1G>A, G235R, G235R, c.704-1G>C,
840 14
843 15 T843A,
837 15
239 12 I239V, I239V ,
230 5 I230V, I230T, I230M,
139 12 p.I137_C139dup,
242 15 A242D,
841 11 p.N841TfsX2, N841K, N841K,
236 6
847 14
192 14
136 14 L136P,
238 12
233 6
838 15
194 12
141 11 I141V, I141N,
135 11 M135V,
128 15 c.381dupT,
225 11 R225W, R225Q,
844 11 L844RfsX3,
243 14
145 14
140 14