SCN5A Variant C373R

Summary of observed carriers, functional annotations, and structural context for SCN5A C373R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

17%

0/10 effective observations

Estimated BrS1 penetrance

38%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

C373R has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 0.882 54 19

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 0 3 – –

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 C373R.
Neighbour residue Distance (Å) Observed variants
364 11
901 8 E901K, S901L,
919 14
363 12
896 12 C896S, C896S,
348 13 P348A,
895 15 L895F,
1417 13
396 14 V396L, V396A,
894 12 I894M,
1715 13
1687 14
372 4
401 14 S401P,
371 8 Q371E,
1711 8 c.5131delG,
904 11 W904X,
366 12
1707 13
365 13
1706 10 Q1706H, Q1706H,
1716 14 p.L1716SfsX71
1714 13 D1714G,
376 7 R376C, R376H,
354 15
897 8 G897R, G897R, G897E,
1423 14 D1423H,
927 15 N927S, N927K, N927K,
369 13 M369K,
1422 12 M1422R,
378 11
1418 11
902 11
349 11 D349N,
373 0
1712 9 G1712S, G1712C,
379 11
898 7
893 10 R893C, R893H,
397 13 I397V, I397F, I397T,
920 15
1709 10 p.T1709del, T1709R, T1709M,
1420 11 G1420R, G1420D, G1420V, G1420P,
900 7
393 13
1713 12
1708 14 T1708I,
1421 11
374 7 W374G,
1705 15
350 13 H350Q, H350Q,
903 12 p.M903CfsX29,
367 6 R367C, R367H, R367L,
370 9 T370M,
879 15 W879R, W879R,
381 14 c.1140+1G>A, c.1141-3C>A,
923 13
905 14
375 6
368 9
899 8
1710 10 S1710L,
380 11
377 8
1419 8 K1419E,
353 12 T353I,
1414 14 Q1414H, Q1414H,