SCN5A Variant V850M

Summary of observed carriers, functional annotations, and structural context for SCN5A V850M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

14%

0/12 effective observations

Estimated BrS1 penetrance

25%

2/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

V850M is present in 2 alleles 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 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 (%)
-2.97 0.999 4.31 0.886 45 18

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 – 2 2 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 V850M.
Neighbour residue Distance (Å) Observed variants
891 6 I891N, I891T,
888 6
848 7 I848F,
223 11 V223L,
856 10 V856L, V856L,
890 10 I890T,
919 12
896 11 C896S, C896S,
895 8 L895F,
842 12
894 9 I894M,
1455 13
1447 13
149 14
926 8
928 14 L928P,
925 10 I925F,
227 12 L227P,
887 9
1451 12 V1451L, V1451D,
886 14 H886P, H886Q, H886Q,
933 15
229 13
851 6 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 13 G897R, G897R, G897E,
924 13 V924I,
927 12 N927S, N927K, N927K,
852 6
854 6 c.2559delT,
224 13 L224F,
845 9 c.2533delG,
857 11 G857D,
902 15
892 8 F892I,
881 13
849 5
226 11 A226G, A226V,
898 15
893 13 R893C, R893H,
921 12
922 8 V922I,
860 15 p.L860fsx89,
920 15
840 15
889 10
843 11 T843A,
930 10 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 13 c.4376_4379delTCTT
858 12 M858L, M858L,
918 12
855 9
1454 14
230 13 I230V, I230T, I230M,
148 13
929 13
1448 14 I1448L, I1448T,
884 10
885 12
847 5
846 6 L846R,
853 5
923 12
883 14
844 11 L844RfsX3,
850 0 V850M, c.2549_2550insTG,
243 14
145 12
861 15 p.F861WfsX90, c.2582_2583delTT,
931 12