SCN5A Variant Q1476R

Summary of observed carriers, functional annotations, and structural context for SCN5A Q1476R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

76%

6/13 effective observations

Estimated BrS1 penetrance

7%

0/13 effective observations

Total carriers

3

0 BrS1 · 3 LQT3 · 0 unaffected

Q1476R has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 3 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-3.82 0.888 -2.22 0.943 3 88

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
24098284 2013 3 3 0 0
Literature, cohort, and gnomAD – 3 0 3 0 –
Variant features alone – 15 12 3 0 – –

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)
24098284 2013 tsA201 93 1.6 6.5 206

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 Q1476R.
Neighbour residue Distance (Å) Observed variants
1328 10 V1328M,
1659 14
1480 6 c.4437+5G>A, c.4438-1C>T,
1773 11
1653 15
1472 7 p.N1472del, N1472S,
1315 14
1777 15 V1777M, V1777L, V1777L
1487 14 M1487L, M1487L, M1487K,
1320 12 M1320I, M1320I, M1320I,
1333 14
1492 14
1656 12
1477 6 K1477N, K1477N,
1471 11
1470 11
1478 7 K1478E,
1660 14 I1660V, I1660S,
1329 9 G1329S,
1769 11
1766 11 M1766L, M1766V, M1766L, M1766T,
1319 10 G1319V,
1774 13 N1774D, c.5321_5324dupACTT,
1479 4
1473 6 F1473S, F1473C,
1468 13 V1468F, V1468A,
1474 7
1324 9
1481 9 G1481R, G1481R, G1481E, G1481V,
1327 10
1318 13
1330 11 A1330T, A1330P, A1330D,
1772 15 L1772V,
1321 10 R1321K,
1323 8 V1323G,
1770 11 I1770V,
1482 10
1322 5 c.3963+2T>C, c.3963+4A>G,
1326 6 A1326S,
1332 14 P1332Q, P1332L,
1467 15
1476 0 Q1476X, Q1476R,
1484 11
1331 14 I1331V,
1475 6 p.Q1475NfsX6, Q1475L,
1469 11 I1469V,
1483 13 Q1483H, Q1483H,
1325 6 N1325S,