SCN5A Variant D872N

Summary of observed carriers, functional annotations, and structural context for SCN5A D872N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/14 effective observations

Estimated BrS1 penetrance

7%

0/14 effective observations

Total carriers

4

0 BrS1 · 0 LQT3 · 4 unaffected

D872N is present in 4 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-0.42 0.999 0.61 0.371 9 0

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 – 4 4 0 0 –
Variant features alone – 15 15 0 0 – –

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 D872N.
Neighbour residue Distance (Å) Observed variants
901 13 E901K, S901L,
870 8
348 13 P348A,
904 14 W904X
871 5
909 12
876 12
868 12 c.2602delC, L868X,
349 11 D349N,
321 12 S321Y,
872 0 D872N,
865 14
323 14
347 15
906 15
351 13 G351S, G351C, G351D, G351V,
874 6 G874D,
878 13 R878C, R878H, R878L,
350 9 H350Q, H350Q,
346 14 E346K, E346G, E346X, E346D, E346D,
877 11
869 13 R869S, R869S,
322 10
905 10
352 15 Y352C,
875 10
908 10
873 4 S873A,