SCN5A Variant G268S

Summary of observed carriers, functional annotations, and structural context for SCN5A G268S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G268S 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 (%)
-5.62 1 -0.74 0.974 6 6

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 G268S.
Neighbour residue Distance (Å) Observed variants
364 9
277 13
271 5 L271V,
266 6 L266H,
276 10 L276Q, L276P,
363 12
1544 15 T1544P,
270 6 Q270K,
360 12
1627 10
396 10 V396L, V396A,
385 12 A385T,
1624 10 V1624I,
355 5 F355I, F355C,
1549 12
391 13
278 14 H278D, H278R,
388 14 I388S,
356 9 D356N,
1543 15 V1543L, V1543L, V1543A,
1542 12
361 7
260 13
366 14
365 8
384 13 S384T,
354 9
386 13 G386R, G386R, G386E,
1546 10 M1546T,
369 14 M369K,
378 14
1545 10
1626 14 R1626C, R1626H, R1626P, R1626L
267 4
1550 12
1625 14
262 10 S262G,
357 10
272 5
397 14 I397V, I397F, I397T,
274 10 G274C,
362 11
261 11
273 8
1628 14
392 7
389 10 Y389H, Y389X,
269 4
1620 11 T1620K, T1620M,
395 11
393 10
394 15
390 15
275 9 N275K, N275K,
264 8
259 15
347 15
382 14
1548 11 E1548K, G1548K,
265 5 A265V,
1619 13 P1619Q, P1619L, c.4856delC,
358 9
367 13 R367C, R367H, R367L,
263 9 V263I,
359 11 A359T, p.A359PfsX12,
1547 13 V1547L, V1547L,
381 10 c.1140+1G>A, c.1141-3C>A,
368 11
380 14
268 0 G268S,
377 12
1622 15
1621 13
353 12 T353I,
1623 10 c.4867delC, R1623X, R1623Q, R1623L,