SCN5A Variant M394I

Summary of observed carriers, functional annotations, and structural context for SCN5A M394I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

20%

1/10 effective observations

Estimated BrS1 penetrance

34%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

M394I has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 1 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 0.477 50 26

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 11 1 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 M394I.
Neighbour residue Distance (Å) Observed variants
403 12
271 14 L271V,
1702 11
1659 15
387 12
396 7 V396L, V396A,
391 5
388 11 I388S,
1698 14 A1698T,
401 11 S401P,
1764 14 c.5290delG, V1764F,
1666 15
371 12 Q371E,
1711 15 c.5131delG,
1707 14
365 13
1704 12 L1704H,
1706 12 Q1706H, Q1706H,
1668 11 M1668T,
386 13 G386R, G386R, G386E,
369 13 M369K,
1767 13 Y1767C
1660 13 I1660V, I1660S,
378 10
1654 15
402 10 F402L, F402L, F402L,
1665 10
267 13
1703 14
1663 14
399 8
272 15
397 7 I397V, I397F, I397T,
1657 13
1759 15 S1759C,
1662 12
1709 11 p.T1709del, T1709R, T1709M,
1701 10 M1701I, M1701I, M1701I,
392 7
389 11 Y389H, Y389X,
395 5
393 6
390 6
394 0
264 11
1708 11 T1708I,
382 12
374 11 W374G,
1705 7
1700 14
1661 10 G1661R, G1661R, G1661E,
381 13 c.1140+1G>A, c.1141-3C>A,
368 11
268 15 G268S,
377 14
398 6
400 10 G400R, G400R, G400E, G400A,
1667 15 V1667I,
1664 10
1658 12