SCN5A Variant F398Y

Summary of observed carriers, functional annotations, and structural context for SCN5A F398Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

31%

1/10 effective observations

Estimated BrS1 penetrance

25%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

F398Y has not been reported 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 2 individuals for Brugada syndrome and 1 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 0.945 29 39

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 12 1 2 – –

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 F398Y.
Neighbour residue Distance (Å) Observed variants
403 7
1659 11
404 11 L404V, L404Q,
1765 13
396 8 V396L, V396A,
1653 12
391 11
1771 12 I1771T
401 8 S401P,
1764 10 c.5290delG, V1764F,
1666 15
371 11 Q371E,
1650 12 L1650F,
260 13
1656 11
365 14
1704 14 L1704H,
1706 14 Q1706H, Q1706H,
1668 12 M1668T,
369 11 M369K,
1767 7 Y1767C,
1660 9 I1660V, I1660S,
378 14
1654 10
1769 14
402 5 F402L, F402L, F402L,
1766 13 M1766L, M1766V, M1766L, M1766T,
1665 12
1768 12 I1768V,
1663 12
399 5
397 6 I397V, I397F, I397T,
405 12
1657 8
1759 13 S1759C,
1662 11
1709 11 p.T1709del, T1709R, T1709M,
1701 14 M1701I, M1701I, M1701I,
392 12
395 7
393 11
394 6
390 12
1770 12 I1770V,
264 12
1651 15
1708 11 T1708I,
374 13 W374G,
1705 10
407 14
1763 12 V1763M, V1763L, V1763L,
1760 15
370 14 T370M,
1661 7 G1661R, G1661R, G1661E,
1655 12
406 11 N406S, N406K, N406K,
368 12
398 0
400 7 G400R, G400R, G400E, G400A,
1667 14 V1667I,
1664 8
1658 8