SCN5A Variant L271V

Summary of observed carriers, functional annotations, and structural context for SCN5A L271V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/11 effective observations

Estimated BrS1 penetrance

14%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

L271V 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 (%)
-2.93 0.999 -0.42 0.921 14 11

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 L271V.
Neighbour residue Distance (Å) Observed variants
328 15
364 13
277 14
271 0 L271V,
266 9 L266H,
276 11 L276Q, L276P,
387 15
270 6 Q270K,
1627 10
396 13 V396L, V396A,
385 9 A385T,
1624 8 V1624I,
355 8 F355I, F355C,
1549 14
391 11
278 13 H278D, H278R,
388 11 I388S,
356 12 D356N,
1542 14
361 11
343 14
365 13
384 11 S384T,
354 12
329 14
386 11 G386R, G386R, G386E,
1546 13 M1546T,
378 14
1545 11
1626 13 R1626C, R1626H, R1626P, R1626L
267 6
1550 13
1625 12
262 14 S262G,
357 13
272 4
274 10 G274C,
273 8
1628 14
392 8
389 7 Y389H, Y389X,
269 7
1620 6 T1620K, T1620M,
395 12
393 11
394 14
390 13
275 8 N275K, N275K,
264 10
382 12
1548 12 E1548K, G1548K,
265 10 A265V,
1619 9 P1619Q, P1619L, c.4856delC,
358 13
263 12 V263I,
381 10 c.1140+1G>A, c.1141-3C>A,
1617 15 p.F1617del,
368 14
380 15
268 5 G268S,
377 14
1622 12
1618 11
1621 10
353 15 T353I,
1623 7 c.4867delC, R1623X, R1623Q, R1623L,