SCN5A Variant Q750R

Summary of observed carriers, functional annotations, and structural context for SCN5A Q750R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

46%

2/11 effective observations

Estimated BrS1 penetrance

14%

1/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

Q750R 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 1 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-1.38 0.049 -0.12 0.633 8 51

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 1 1 – –

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)
25904541 2015 HEK 48 3 -2 114
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 Q750R.
Neighbour residue Distance (Å) Observed variants
758 13 G758E,
742 13 T742A,
811 10 R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT,
733 10 F733L,
741 11 p.M741_T742delinsI ,
808 10 R808P, R808H, R808C,
745 11
746 8 E746K,
760 15 p.F760SfsX5,
759 14 c.2274delG, p.I759FfsX6, I759V,
792 12
755 9
800 10 R800L, R800H, R800C,
754 6
797 12 G797V,
737 11
750 0 Q750R,
749 6
743 11
798 14
793 14 L793F,
747 6 E747A,
735 14 A735V, A735E, A735T,
732 15
734 12 c.2201dupT, M734V,
756 11
814 14 R814Q,
807 15
757 10
1354 14
744 12
752 6 G752R,
751 5 V751I, V751F,
796 9
802 14
736 13 L736P,
730 12 N730K,
753 5
729 15 p.L729del,
795 10
748 8 M748I,
799 9