SCN5A Variant M1422R

Summary of observed carriers, functional annotations, and structural context for SCN5A M1422R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

26%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

M1422R is present in 1 alleles 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 2 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 (%)
-5.42 1 -4.01 0.971 33 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 – 1 1 0 0 –
Variant features alone – 15 13 0 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 M1422R.
Neighbour residue Distance (Å) Observed variants
891 13 I891N, I891T,
880 13
888 13
890 10 I890T,
901 9 E901K, S901L,
896 10 C896S, C896S,
895 13 L895F,
1417 12
1430 13 D1430N,
1426 8
894 12 I894M,
1453 14
1715 14
1447 12
1444 13 L1444I,
372 13
1440 13 W1440X,
1449 14 Y1449S, Y1449C,
1429 11
1711 14 c.5131delG,
1450 10
887 14
1398 14 V1398M,
1411 12
1451 13 V1451L, V1451D,
886 12 H886P, H886Q, H886Q,
1458 14 S1458Y,
1714 11 D1714G
376 15 R376C, R376H,
897 11 G897R, G897R, G897E,
1423 5 D1423H,
1431 15 S1431C,
1422 0 M1422R,
1418 9
902 11
892 10 F892I,
373 12
1712 13 G1712S, G1712C,
1356 15 c.4066_4068delTT,
898 8
893 6 R893C, R893H,
1412 13 L1412F,
889 9
1420 6 G1420R, G1420D, G1420V, G1420P,
900 13
1360 14 F1360C,
1425 5
1713 15
1454 12
1427 10 A1427S, A1427E,
1446 15
1424 7 I1424V,
1448 15 I1448L, I1448T,
878 7 R878C, R878H, R878L,
1400 12 V1400I,
1421 4
885 15
1416 12 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
877 12
879 6 W879R, W879R,
905 14
375 14
899 14
1710 15 S1710L,
1415 9
1428 10 A1428S, A1428V,
1419 9 K1419E,
1414 10 Q1414H, Q1414H,
1402 15
1413 14