SCN5A Variant M1701I

Summary of observed carriers, functional annotations, and structural context for SCN5A M1701I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/12 effective observations

Estimated BrS1 penetrance

8%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

M1701I 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 0 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 (%)
-3.7 0.766 2.48 0.853 7 1

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
28701297 2017 1 0 0 1 DCM
Literature, cohort, and gnomAD – 2 2 0 0 –
Variant features alone – 15 15 0 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
28701297 2017

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 M1701I.
Neighbour residue Distance (Å) Observed variants
1702 5
387 9
391 12
388 12 I388S,
1698 5 A1698T,
1220 13 G1220E,
1673 10
1675 12
1666 11
1711 14 c.5131delG,
1707 10
1694 10
1704 6 L1704H,
1226 13
1706 10 Q1706H, Q1706H,
1695 13 Q1695X,
1716 14 p.L1716SfsX71,
1688 15
1669 8
1671 11
1668 5 M1668T,
1676 10 M1676I, M1676I, M1676T, M1676I,
1692 11
386 13 G386E, G386R, G386R,
1219 14 S1219N,
1672 7 S1672Y,
1693 11
1699 7
378 11
331 13
1665 8
379 14
1703 7
1663 14
397 15 I397T, I397V, I397F,
1759 14 S1759C,
1662 14
1709 13 T1709M, p.T1709del, T1709R,
1701 0 M1701I, M1701I, M1701I,
1307 15
1228 15 Y1228C, Y1228F, Y1228H,
1223 10 c.3667delG,
1755 12
1697 7
389 14 Y389X, Y389H,
1222 14 p.L1222LfsX7, L1222R,
1227 15
393 13
1674 14 F1674V,
390 8
394 10
1708 10 T1708I,
382 12
1696 9
374 14 W374G,
1705 6
1700 5
1751 14
1677 15
1752 14
1224 12
1670 11
1661 13 G1661R, G1661R, G1661E,
1691 12
1679 14
398 14
1667 10 V1667I,
1664 11