SCN5A Variant Y389F

Summary of observed carriers, functional annotations, and structural context for SCN5A Y389F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/10 effective observations

Estimated BrS1 penetrance

15%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Y389F has not been reported in gnomAD. This residue resides in a Mild_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 (%)
NA NA NA 0.921 12 2

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 – 0 0 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 Y389F.
Neighbour residue Distance (Å) Observed variants
328 12
333 13 c.998+1G>A, c.998+5G>A,
271 7 L271V,
1702 11
266 15 L266H,
326 15
276 11 L276Q, L276P,
387 8
270 13 Q270K,
396 12 V396L, V396A,
385 6 A385T,
1624 12 V1624I,
355 11 F355I, F355C,
391 7
330 11 S330F,
278 13 H278D, H278R,
388 4 I388S,
1698 13 A1698T,
332 10 A332T,
365 14
327 12
384 9 S384T,
354 15
329 10
1692 14
386 5 G386R, G386R, G386E,
378 9
1699 14
331 12
267 11
379 13
272 7
397 14 I397V, I397F, I397T,
274 13 G274C,
273 13
1701 14 M1701I, M1701I, M1701I
325 14 L325R,
392 7
389 0 Y389H, Y389X,
269 13
1620 10 T1620K, T1620M,
395 11
393 8
394 11
390 7
275 10 N275K, N275K,
383 12
264 13
382 7
265 14 A265V,
1619 13 P1619Q, P1619L, c.4856delC,
374 14 W374G,
1705 13
381 7 c.1140+1G>A, c.1141-3C>A,
1691 13
368 14
380 12
268 10 G268S,
377 12
1618 14
1621 11
1623 13 c.4867delC, R1623X, R1623Q, R1623L,