SCN5A Variant G1358R

Summary of observed carriers, functional annotations, and structural context for SCN5A G1358R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

34%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G1358R is present in 1 alleles 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 (%)
-7.8 1 -5.12 0.937 49 0

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 – 1 1 0 0 –
Variant features alone – 15 12 0 3 – –

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 G1358R.
Neighbour residue Distance (Å) Observed variants
1355 9
1403 6
1357 4 A1357V,
742 15 T742A,
741 10 p.M741_T742delinsI ,
1430 12 D1430N,
808 15 R808C, R808H, R808P,
1352 10
1406 14 G1406R, G1406R, G1406E,
1361 7
746 15 E746K,
1351 14 M1351V, M1351R,
739 5
1395 10
1397 9 c.4189delT, c.4190delA,
1350 14 I1350T, I1350L,
1429 14
1398 10 V1398M,
1411 14
1353 9 V1353M
1407 12
737 11
1358 0 G1358R, G1358W, G1358R,
1396 12
1362 11 R1362S, c.4083delG, R1362S,
1433 7 G1433W, G1433R, G1433R, G1433V,
1438 11 P1438L,
1388 13
1404 10
1437 12
1349 14
1431 8 S1431C,
1359 4 K1359M, K1359N, K1359N,
1356 8 c.4066_4068delTT,
1434 5 c.4299+1G>T, c.4300-1G>A, c.4299G>A, c.4299_4300insG, c.4300-2A>T, c.4299+2T>A, c.4299+28C>T, c.4299+1delG, c.4299delG, Y1434X,
1408 12 G1408R, G1408R,
1435 8
1360 7 F1360C,
1401 9
1399 15
1354 10
1427 11 A1427S, A1427E,
1446 15
1424 14 I1424V,
738 9
1432 12 R1432S, R1432S, R1432G,
1389 14
1439 15 Q1439H, Q1439H, Q1439R,
1405 13 V1405M, V1405L, V1405L,
740 9 p.N740del,
1400 12 V1400I,
1443 14 N1443S,
736 14 L736P,
1428 11 A1428S, A1428V,
1363 14 C1363Y,
1436 10
1402 9