SCN5A Variant p.M903CfsX29

Summary of observed carriers, functional annotations, and structural context for SCN5A p.M903CfsX29. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

18%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

p.M903CfsX29 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 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 None 23 6

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 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 p.M903CfsX29.
Neighbour residue Distance (Å) Observed variants
364 11
891 12 I891N, I891T,
880 15
890 11 I890T,
901 8 E901K, S901L,
919 5
862 15
363 8
896 15 C896S, C896S,
348 15 P348A,
895 14 L895F,
360 10
894 9 I894M,
372 10
361 14
904 5 W904X,
366 11
887 14
365 14
864 14
376 14 R376C, R376H,
354 14
897 12 G897R, G897R, G897E,
924 14 V924I
909 11
857 13 G857D,
902 5
349 12 D349N,
373 12
881 12
898 11
893 11 R893C, R893H,
921 12
922 11 V922I,
860 14 p.L860fsx89,
362 13
911 10 G911E,
920 8
900 5
918 9
917 9 L917V, L917R,
865 13
913 10
916 6
912 9 Q912R,
347 15
906 6
351 12 G351S, G351C, G351D, G351V,
910 10 S910L,
350 9 H350Q, H350Q,
903 0 p.M903CfsX29,
367 9 R367C, R367H, R367L,
359 13 A359T, p.A359PfsX12,
853 14
370 12 T370M,
877 14
879 14 W879R, W879R,
923 11
905 7
352 9 Y352C,
915 6 C915R,
368 15
899 6
377 14
908 10
914 10
861 11 p.F861WfsX90, c.2582_2583delTT,
353 11 T353I,
907 5