SCN5A Variant D372A

Summary of observed carriers, functional annotations, and structural context for SCN5A D372A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

26%

1/10 effective observations

Estimated BrS1 penetrance

29%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

D372A 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 0.962 38 33

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 D372A.
Neighbour residue Distance (Å) Observed variants
364 9
891 14 I891N, I891T,
890 14 I890T,
919 12
901 9 E901K, S901L,
363 10
896 11 C896S, C896S,
895 12 L895F,
1417 13
396 13 V396L, V396A,
894 9 I894M,
355 15 F355I, F355C,
372 0
401 11 S401P,
926 15
371 6 Q371E,
1711 10 c.5131delG,
928 13 L928P,
361 14
904 11 W904X,
366 9
365 11
1706 12 Q1706H, Q1706H,
376 10 R376C, R376H,
897 6 G897R, G897R, G897E,
924 14 V924I,
927 12 N927S, N927K, N927K,
369 10 M369K,
1422 13 M1422R,
378 13
1418 11
902 10
402 14 F402L, F402L, F402L,
892 15 F892I,
349 13 D349N,
373 4
1712 12 G1712S, G1712C
379 14
898 6
893 9 R893C, R893H,
922 13 V922I,
397 11 I397V, I397F, I397T,
405 13
362 14
261 15
920 12
1709 11 p.T1709del, T1709R, T1709M,
1420 13 G1420R, G1420D, G1420V, G1420P,
900 6
393 13
1713 14
916 14
1708 15 T1708I,
1421 12
374 8 W374G,
350 14 H350Q, H350Q,
903 10 p.M903CfsX29,
367 4 R367C, R367H, R367L,
1760 15
370 6 T370M,
923 9
905 14
375 9
368 8
899 5
1710 11 S1710L,
380 14
377 9
400 14 G400R, G400R, G400E, G400A,
1419 10 K1419E,
353 12 T353I,
907 15