SCN5A Variant R104L

Summary of observed carriers, functional annotations, and structural context for SCN5A R104L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

25%

1/10 effective observations

Estimated BrS1 penetrance

37%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

R104L has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
NA NA NA 0.979 51 31

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 – 0 0 0 0 –
Variant features alone – 15 11 1 3 – –

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 R104L.
Neighbour residue Distance (Å) Observed variants
89 15
90 14 p.Q90WfsX14,
91 14
92 13 c.274-24C>T, T92I,
93 13 F93S,
94 12 I94V, I94S,
95 11 V95I, V95L, V95L,
96 11
97 10
98 9
99 8
100 8
101 7 T101I,
102 5
103 4
104 0 R104G, R104W, R104Q,
105 4
106 5 S106T,
107 7
108 8
109 8 N109K, N109K,
110 9 A110T,
111 10
112 11 Y112C,
113 11 V113I, V113A,
114 12
115 13 S115G,
116 13
117 14
118 14
119 15 P119S, P119L