SCN5A Variant L266H

Summary of observed carriers, functional annotations, and structural context for SCN5A L266H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

L266H is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_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 (%)
-6.83 1 -6.07 0.983 2 4

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 L266H.
Neighbour residue Distance (Å) Observed variants
364 12
271 9 L271V,
266 0 L266H,
363 14
1544 10 T1544P,
270 6 Q270K,
360 14
1627 7
396 13 V396L, V396A,
1624 9 V1624I,
355 9 F355I, F355C,
1549 12
1538 12
356 11 D356N,
1543 9 V1543L, V1543L, V1543A,
1542 6
361 8
260 11
366 15
365 10
1564 14
258 12 V258A,
354 13
1546 5 M1546T,
1545 6
1630 11 I1630V, I1630R,
1626 10 R1626C, R1626H, R1626P, R1626L,
267 5
1550 14
1625 13
1560 14 L1560F, L1560F,
262 6 S262G,
357 10
272 10
274 14 G274C,
362 10
261 10
273 10
1628 11
1539 12 C1539Y, C1539F,
392 11
389 15 Y389H, Y389X,
269 5
1620 12 T1620K, T1620M,
395 13
393 15
275 14 N275K, N275K,
264 8
259 11
1548 9 E1548K, G1548K,
265 4 A265V,
1619 14 P1619Q, P1619L, c.4856delC,
358 7
263 6 V263I,
359 11 A359T, p.A359PfsX12,
1629 13 R1629G, R1629X, R1629Q,
1547 10 V1547L, V1547L,
1541 10
1540 13
1631 14 G1631D
368 14
268 6 G268S,
1622 13
257 15
1621 14
1623 9 c.4867delC, R1623X, R1623Q, R1623L,