SCN5A Variant L1217I

Summary of observed carriers, functional annotations, and structural context for SCN5A L1217I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/10 effective observations

Estimated BrS1 penetrance

25%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L1217I has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 0.848 31 7

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
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 13 0 2 – –

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

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 L1217I.
Neighbour residue Distance (Å) Observed variants
1245 10 M1245I, M1245I, M1245I,
1218 4 S1218I, S1218T,
1217 0
1243 13 D1243N,
1216 6 L1216V,
1220 6 G1220E,
1673 15
1213 5
1210 10 F1210S,
1241 12
1309 12 R1309H, R1309C,
1669 13
1221 7 A1221V,
1242 10
1219 6 S1219N,
1313 14
1239 11 L1239P,
1310 12
1306 11 R1306S, R1306H,
1246 8
1235 14
1247 14 T1247I,
1307 12
1223 11 c.3667delG,
1222 9 L1222R, p.L1222LfsX7,
1215 7 I1215V,
1206 15
1214 6 M1214T,
1212 10 p.I1212del,
1253 15 E1253G,
1211 10
1250 13
1224 11
1209 12 T1209R,
1240 15 E1240Q,
1225 14 E1225K, G1225K,
1238 12
1249 12 V1249D,
1303 14 R1303W, R1303Q,