SCN5A Variant R975Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R975Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/21 effective observations

Estimated BrS1 penetrance

7%

1/21 effective observations

Total carriers

11

0 BrS1 · 0 LQT3 · 11 unaffected

R975Q is present in 11 alleles in gnomAD. This residue resides in a Mild_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 (%)
-0.99 0.999 -0.07 0.512 13 5

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 – 11 11 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 R975Q.
Neighbour residue Distance (Å) Observed variants
960 15 Q960K,
961 14
962 14
963 13
964 13 A964G,
965 12 R965C, R965H, R965L,
966 11
967 11 Q967R,
968 10
969 9 G969C, G969S,
970 8
971 8 R971C, R971H,
972 7 c.2914_2923delTTTGTCAAGC,
973 5
974 4 K974D,
975 0 R975W, R975Q,
976 4
977 5
978 7
979 8 D979H,
980 8
981 9 C981F,
982 10 C982R,
983 11 G983D,
984 11
985 12
986 13 R986L, R986W, R986Q,
987 13
988 14 R988Q, R988W,
989 14
990 15