SCN5A Variant E375V

Summary of observed carriers, functional annotations, and structural context for SCN5A E375V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/10 effective observations

Estimated BrS1 penetrance

35%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

E375V 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 0.944 47 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 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 E375V.
Neighbour residue Distance (Å) Observed variants
364 13
1702 11
901 12 E901K, S901L,
276 15 L276Q, L276P,
348 13 P348A,
1417 14
1715 9
1687 9
372 9
371 10 Q371E,
1711 5 c.5131delG,
904 15 W904X,
1707 10
1704 12 L1704H,
1706 6 Q1706H, Q1706H,
1716 9 p.L1716SfsX71,
1714 11 D1714G,
376 5 R376C, R376H,
1688 12
897 14 G897R, G897R, G897E,
1423 14 D1423H,
1692 10
386 15 G386R, G386R, G386E,
1422 14 M1422R,
1693 15
378 7
1699 14
1418 14
349 12 D349N,
373 6
1712 6 G1712S, G1712C,
379 6
1703 10
898 12
893 15 R893C, R893H,
397 13 I397V, I397F, I397T,
1719 14
1709 10 p.T1709del, T1709R, T1709M,
325 14 L325R,
1420 12 G1420R, G1420D, G1420V, G1420P,
900 12
324 14
393 11
1713 10
390 14
383 12
1708 12 T1708I,
382 11
1421 14
1718 14 S1718R, S1718R, S1718R
374 6 W374G,
1705 11
1689 12 D1689N,
1700 15
1717 13 L1717P,
367 10 R367C, R367H, R367L,
370 13 T370M,
1752 14
381 11 c.1140+1G>A, c.1141-3C>A,
1686 11
375 0
1691 13
368 11
899 14
1710 9 S1710L,
380 9
377 7
1685 15
1419 9 K1419E,
353 13 T353I,
1414 14 Q1414H, Q1414H,