SCN5A Variant G969C

Summary of observed carriers, functional annotations, and structural context for SCN5A G969C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/12 effective observations

Estimated BrS1 penetrance

10%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

G969C is present in 2 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 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 (%)
-7.32 1 -2.04 0.803 5 3

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 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 G969C.
Neighbour residue Distance (Å) Observed variants
954 15 R954G,
955 14 p.E955DfsX74,
956 14 M956I, M956I, M956I, M956T,
957 13
958 13
959 12 L959P,
960 11 Q960K,
961 11
962 10
963 9
964 8 A964G,
965 8 R965C, R965L, R965H,
966 7
967 5 Q967R,
968 4
969 0 G969C, G969S,
970 4
971 5 R971C, R971H,
972 7 c.2914_2923delTTTGTCAAGC,
973 8
974 8 K974D,
975 9 R975Q, R975W,
976 10
977 11
978 11
979 12 D979H,
980 13
981 13 C981F,
982 14 C982R,
983 14 G983D,
984 15