SCN5A Variant T1304M

Summary of observed carriers, functional annotations, and structural context for SCN5A T1304M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

22%

15/77 effective observations

Estimated BrS1 penetrance

4%

3/77 effective observations

Total carriers

67

2 BrS1 · 15 LQT3 · 50 unaffected

T1304M is present in 46 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-5.3 1 0.36 0.924 7 12

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
24613995 2014 1 0 0 1 irritable bowel syndrome
17210841 2007 1 0 0 1 SIDS
10508990 1999 6 5 0 0
10961955 2000 1 1 0 0
10973849 2000 1 1 0 0
22360817 2012 3 3 0 0
23631430 2013 1 1 0 0
24144883 2014 1 0 0 1 AF
24631775 2014 1 0 0 1 SIDS
25210526 2014 2 0 2 0
26669661 2016 4 2 0 0
26746457 2016 1 0 0 0
27566755 2016 9 9 0 0
22685113 2012 1 0 0 1 AF
19716085 2009 3 3 0 0
29325976 2018 1 0 1 0
29764897 2018 1 0 0 0
30059973 2018 2 2 0 0
Literature, cohort, and gnomAD – 67 50 15 2 –
Variant features alone – 15 14 0 1 – –

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)
24613995 2014 HEK 68 -0.3 0.6 81
18451998 2008 tsA201 100
17210841 2007 tsA206 100 6.7 11.2 718
10508990 1999
10961955 2000
10973849 2000
22360817 2012
23631430 2013
24144883 2014
24631775 2014
25210526 2014
26669661 2016
29017927 2017
26746457 2016
27566755 2016
28412158 2017
17646591 2007
22685113 2012 HEK
19716085 2009
29325976 2018
29764897 2018
30059973 2018

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 T1304M.
Neighbour residue Distance (Å) Observed variants
1218 11 S1218T, S1218I,
1281 9 c.3840+1G>A, V1281F,
1304 0 T1304M,
1243 11 D1243N,
1274 12
1216 14 L1216V,
1285 12
1299 12 c.3894delC,
1220 12 G1220E,
1673 6
1675 9
1283 15 L1283M,
1309 11 R1309C, R1309H,
1226 11
1747 15 V1747M
1669 10
1671 10
1221 12 A1221V,
1242 13
1668 15 M1668T,
1676 10 M1676T, M1676I, M1676I, M1676I,
1219 10 S1219N,
1672 10 S1672Y,
1279 13 V1279I,
1239 12 L1239P,
1310 12
1306 7 R1306S, R1306H,
1305 4
1680 15 A1680T, A1680P,
1246 13
1282 11 S1282A,
1302 6 p.L1302Vfs18,
1247 14 T1247I,
1307 6
1678 10 N1678S,
1223 11 c.3667delG,
1697 15
1275 13 D1275N,
1222 8 p.L1222LfsX7, L1222R,
1300 10
1674 7 F1674V,
1215 12 I1215V,
1301 5
1284 13
1700 15
1280 14
1751 13
1311 13 L1311P,
1677 8
1308 7 L1308F,
1250 13
1224 14
1670 8
1240 13 E1240Q,
1225 10 E1225K, G1225K,
1278 9 I1278N,
1679 13
1277 12
1667 13 V1667I,
1303 6 R1303W, R1303Q,
1666 13