SCN5A Variant V751I

Summary of observed carriers, functional annotations, and structural context for SCN5A V751I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/14 effective observations

Estimated BrS1 penetrance

7%

0/14 effective observations

Total carriers

4

0 BrS1 · 0 LQT3 · 4 unaffected

V751I 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 (%)
-0.58 0.101 3.37 0.614 9 10

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
29544605 2018 1 0 0 1 SIDS
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.

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)
29544605 2018

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 V751I.
Neighbour residue Distance (Å) Observed variants
758 11 G758E,
742 14 T742A,
811 13 R811H, c.2435_2436+3delTGGTAinsCGCCT, R811G,
733 9 F733L,
741 14 p.M741_T742delinsI ,
808 14 R808C, R808P, R808H,
745 11
746 10 E746K,
760 14 p.F760SfsX5,
759 12 p.I759FfsX6, c.2274delG, I759V,
792 14
755 6
731 15 T731I,
800 13 R800C, R800L, R800H,
754 5
726 13
737 14
750 5 Q750R,
749 7
743 12
747 6 E747A,
732 14
734 13 M734V, c.2201dupT,
756 8
814 15 R814Q,
757 10
744 12
752 4 G752R,
751 0 V751I, V751F,
796 12
736 14 L736P
730 11 N730K,
753 6
729 12 p.L729del,
795 14
748 6 M748I,
799 14