SCN5A Variant M1320I

Summary of observed carriers, functional annotations, and structural context for SCN5A M1320I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/12 effective observations

Estimated BrS1 penetrance

14%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

M1320I is present in 2 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 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 (%)
-3.54 0.947 1.31 0.94 19 6

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 – 2 2 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 M1320I.
Neighbour residue Distance (Å) Observed variants
1328 11 V1328M,
1659 5
1271 13 W1271C, W1271C,
1480 13 c.4437+5G>A, c.4438-1C>T,
1653 13
1315 5
1314 5 c.3940_3941delCT,
1320 0 M1320I, M1320I, M1320I,
1764 15 V1764F, c.5290delG,
1666 11
1656 8
1477 13 K1477N, K1477N,
1762 14 I1762M, p.I1762del,
1767 12 Y1767C,
1313 9
1660 7 I1660S, I1660V,
1654 14
1329 14 G1329S,
1310 12
1769 14
1316 10 R1316Q, R1316L,
1766 10 M1766V, M1766L, M1766T, M1766L,
1319 4 G1319V,
1665 13
1479 15
1473 12 F1473C, F1473S,
1663 7
1657 10
1662 7
1324 6
1317 6 F1317C,
1327 10
1758 15 p.I1758del, I1758V,
1318 8
1330 15 A1330P, A1330D, A1330T,
1321 7 R1321K,
1323 4 V1323G,
1770 12 I1770V,
1212 15 p.I1212del,
1322 6 c.3963+2T>C, c.3963+4A>G,
1312 10
1326 10 A1326S,
1763 11 V1763L, V1763L, V1763M,
1311 10 L1311P,
1476 12 Q1476R, Q1476X,
1661 9 G1661R, G1661R, G1661E,
1655 10
1469 15 I1469V,
1325 9 N1325S,
1667 13 V1667I,
1664 11
1658 10