SCN5A Variant Q960K

Summary of observed carriers, functional annotations, and structural context for SCN5A Q960K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

59%

3/11 effective observations

Estimated BrS1 penetrance

6%

0/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

Q960K has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-3.73 0.997 1.55 0.815 2 64

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
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
Variant features alone – 15 13 2 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
19716085 2009

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 Q960K.
Neighbour residue Distance (Å) Observed variants
945 15 D945G,
946 14
947 14
948 13
949 13
950 12 P950X,
951 11 D951X, c.2850delT,
952 11 E952K,
953 10 D953E, D953Y, D953E,
954 9 R954G,
955 8 p.E955DfsX74,
956 8 M956I, M956I, M956I, M956T,
957 7
958 5
959 4 L959P,
960 0 Q960K,
961 4
962 5
963 7
964 8 A964G
965 8 R965C, R965H, R965L,
966 9
967 10 Q967R,
968 11
969 11 G969C, G969S,
970 12
971 13 R971C, R971H,
972 13 c.2914_2923delTTTGTCAAGC,
973 14
974 14 K974D,
975 15 R975Q, R975W,