SCN5A Variant M390I

Summary of observed carriers, functional annotations, and structural context for SCN5A M390I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/10 effective observations

Estimated BrS1 penetrance

20%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

M390I 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 0.854 23 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 M390I.
Neighbour residue Distance (Å) Observed variants
333 15 c.998+1G>A, c.998+5G>A,
271 13 L271V,
1702 7
387 7
396 11 V396L, V396A,
385 11 A385T,
391 5
330 13 S330F,
388 6 I388S,
1698 9 A1698T,
332 13 A332T,
1707 14
1704 11 L1704H,
1706 11 Q1706H, Q1706H,
384 14 S384T,
1669 15
329 14
1668 11 M1668T,
1692 12
386 8 G386R, G386R, G386E,
1672 14 S1672Y,
1693 15
378 8
1699 10
331 12
402 15 F402L, F402L, F402L,
1665 11
267 15
379 12
1703 11
399 13
272 13
397 11 I397V, I397F, I397T,
1709 14 p.T1709del, T1709R, T1709M
1701 8 M1701I, M1701I, M1701I,
392 8
1697 12
389 7 Y389H, Y389X,
395 9
393 7
390 0
394 6
383 14
264 14
1708 13 T1708I,
382 8
1696 14
374 12 W374G,
1705 7
1700 11
1661 14 G1661R, G1661R, G1661E,
381 10 c.1140+1G>A, c.1141-3C>A,
375 14
1691 12
368 13
380 15
268 15 G268S,
377 13
398 12
1664 13