SCN5A Variant A265V

Summary of observed carriers, functional annotations, and structural context for SCN5A A265V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

9%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

A265V is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-3.9 1 -4.62 0.966 2 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 15 0 0 – –

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 A265V.
Neighbour residue Distance (Å) Observed variants
364 8
271 10 L271V,
266 4 L266H,
276 14 L276Q, L276P,
363 10
1544 14 T1544P,
270 9 Q270K,
360 11
1627 10
396 10 V396L, V396A,
1624 12 V1624I,
355 7 F355I, F355C,
1549 13
401 15 S401P,
356 11 D356N,
1543 12 V1543L, V1543L, V1543A,
1542 10
361 5
260 9
366 11
365 6
258 10 V258A,
354 11
1546 8 M1546T,
369 11 M369K,
1545 10
1630 13 I1630V, I1630R
1626 14 R1626C, R1626H, R1626P, R1626L,
267 6
1550 15
262 5 S262G,
357 9
256 14
399 14
272 10
397 14 I397V, I397F, I397T,
274 14 G274C,
362 6
261 7
273 11
1628 13
1539 15 C1539Y, C1539F,
392 9
389 14 Y389H, Y389X,
269 6
1620 15 T1620K, T1620M,
395 12
393 12
275 14 N275K, N275K,
264 6
259 10
1548 12 E1548K, G1548K,
265 0 A265V,
358 6
367 12 R367C, R367H, R367L,
263 6 V263I,
359 9 A359T, p.A359PfsX12,
1547 12 V1547L, V1547L,
370 15 T370M,
1541 14
381 14 c.1140+1G>A, c.1141-3C>A,
368 10
268 5 G268S,
377 13
257 12
400 13 G400R, G400R, G400E, G400A,
353 13 T353I,
1623 12 c.4867delC, R1623X, R1623Q, R1623L,