SCN5A Variant I1630V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1630V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/11 effective observations

Estimated BrS1 penetrance

13%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1630V is present in 1 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 (%)
-0.92 0.943 3.89 0.67 20 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
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

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 I1630V.
Neighbour residue Distance (Å) Observed variants
266 11 L266H,
1544 13 T1544P,
270 15 Q270K,
1627 7
1567 14 F1567L, F1567L, F1567L,
1624 11 V1624I,
1536 11
1538 6
1531 13
1635 10
1634 8 L1634P
1543 11 V1543L, V1543L, V1543A,
1534 11
1542 6
260 10
1571 13 F1571C,
258 13 V258A,
1546 12 M1546T,
1545 11
1630 0 I1630V, I1630R,
1532 13 V1532I, V1532F,
1626 10 R1626C, R1626H, R1626P, R1626L,
267 11
1625 11
262 9 S262G,
256 12
399 15
261 13
1628 6
1589 14
1632 6 R1632C, R1632H, R1632L,
1539 7 C1539Y, C1539F,
1597 15 V1597M,
255 14
395 15
1535 7
1537 11
1594 11 F1594S,
264 11
259 7
1633 6
1591 9 W1591X,
1593 15 I1593M,
1595 11
265 13 A265V,
1637 12
1636 10
263 7 V263I,
1629 6 R1629G, R1629X, R1629Q,
1574 14 c.4719C>T, E1574K,
1533 14 T1533I,
1541 9
1592 13
1540 11
1631 4 G1631D,
1590 13
1622 15
1647 14
257 14
1598 13 V1598A,
1623 14 c.4867delC, R1623X, R1623Q, R1623L,