SCN5A Variant M414R

Summary of observed carriers, functional annotations, and structural context for SCN5A M414R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

19%

0/10 effective observations

Estimated BrS1 penetrance

13%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

M414R has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 0.91 9 23

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 14 0 1 – –

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 M414R.
Neighbour residue Distance (Å) Observed variants
414 0 M414V,
939 12 L939F,
1643 14 I1643L,
937 14
1778 10
1773 12
249 7 K249X,
247 12 V247L, V247L,
1771 13 I1771T,
1777 11 V1777L, V1777L, V1777M,
418 6 E418K,
250 10
409 9 L409P, L409V,
928 15 L928P,
1650 15 L1650F,
417 7
933 11
246 8
935 13 L935P,
1779 7 T1779M,
412 6 V412D,
1470 14
245 9 Q245K,
1776 7
244 13
1769 14
415 4 A415T,
1649 13 A1649V,
1768 15 I1768V,
940 13 S940N,
1774 13 N1774D, c.5321_5324dupACTT,
405 15
420 11
248 12
241 12
419 10 Q419X,
1781 13 E1781G, E1781D, E1781D,
930 15 c.2788-6C>T, c.2787+17_2787+18insACACACACACACACACACACACA,
1772 10 L1772V,
1645 12 T1645M,
239 14 I239V , I239V,
251 14
410 6 A410V,
1780 9 E1780G,
242 10 A242D,
929 13
416 9 Y416C,
413 5 A413E, A413T,
408 10
253 12
407 10
1783 11
936 10
238 14
422 13
1775 7 F1775V, p.F1775LfsX15,
1642 12 G1642E,
421 11
406 13 N406K, N406S, N406K,
252 13
411 5 V411M,
243 13
932 12
1646 11
1489 15 E1489D, E1489D,
1782 11