SCN5A Variant L177M

Summary of observed carriers, functional annotations, and structural context for SCN5A L177M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

54%

5/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L177M 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 5 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 0.723 84 0

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 10 0 5 – –

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 L177M.
Neighbour residue Distance (Å) Observed variants
170 10 F170I,
126 12 K126E,
175 8 K175N, K175N,
113 10 V113I, V113A,
129 13
194 14
188 11
178 5 A178G,
128 10 c.381dupT,
117 14
179 8 R179X, R179Q,
119 11 P119S, P119L,
169 12
177 0 L177P,
123 9 A123G, A123V,
121 6 R121W, R121Q,
198 13
127 10
124 6 A124D,
118 9
125 8 V125L, V125L,
181 8
176 5
172 8
174 5 V174I,
185 11 A185T, A185V,
133 13
115 10 S115G,
182 12 C182R, C182Y,
173 5
112 12 Y112C,
114 7
184 10 H184R,
116 11
187 14 T187S, T187S, T187I
180 6 G180V,
120 8
183 13
122 11
171 11