SCN5A Variant I127V

Summary of observed carriers, functional annotations, and structural context for SCN5A I127V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

45%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I127V 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 4 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 0.375 70 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 – 0 0 0 0 –
Variant features alone – 15 11 0 4 – –

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 I127V.
Neighbour residue Distance (Å) Observed variants
171 10
126 6 K126E,
136 11 L136P,
175 10 K175N, K175N,
129 7
135 12 M135V,
167 13
178 9 A178G,
128 5 c.381dupT,
179 12 R179X, R179Q
119 13 P119S, P119L,
169 15
177 10 L177P,
123 6 A123G, A123V,
121 11 R121W, R121Q,
127 0
124 5 A124D,
118 15
125 6 V125L, V125L,
176 13
172 12
131 10
174 7 V174I,
133 6
173 11
132 9 c.393-5C>A,
130 6
134 9 N134S,
170 9 F170I,
120 11
122 11
137 12 I137V,