SCN5A Variant M715I

Summary of observed carriers, functional annotations, and structural context for SCN5A M715I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

M715I is present in 1 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 (%)
-3.2 0.013 -1.44 0.735 2 1

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 – 1 1 0 0 –
Variant features alone – 15 15 0 0 – –

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 M715I.
Neighbour residue Distance (Å) Observed variants
719 10
723 15 I723V,
710 9
766 14
715 0 M715I, M715I, M715T, M715I,
713 7
712 5
763 14 E763D, E763D, E763K
767 10
772 15 D772N,
717 9 P717L,
770 10
775 14
771 10 L771V,
720 10
769 14
722 15
714 5 V714D, V714A,
776 14 p.Y776del,
768 15
721 14
716 6
711 5
718 11 F718L, F718L, F718L,
779 15 Q779K, Q779X,
782 15 N782T,