SCN5A Variant c.2850delT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.2850delT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

45%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.2850delT has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
NA NA NA None 57 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
20129283 2010 1 0 1 0
29325976 2018 2 0 2 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 12 0 3 – –

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)
29325976 2018
20129283 2010

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 c.2850delT.
Neighbour residue Distance (Å) Observed variants
936 15
937 14
938 14
939 13 L939F,
940 13 S940N,
941 12 S941F, S941N,
942 11
943 11 S943N,
944 10
945 9 D945G,
946 8
947 8
948 7
949 5
950 4 P950X,
951 0 D951X, c.2850delT,
952 4 E952K,
953 5 D953E, D953Y, D953E,
954 7 R954G,
955 8 p.E955DfsX74,
956 8 M956I, M956I, M956I, M956T,
957 9
958 10
959 11 L959P,
960 11 Q960K,
961 12
962 13
963 13
964 14 A964G,
965 14 R965C, R965H, R965L,
966 15