KCNQ1 Variant V418I

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V418I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

2/34 effective observations

Total carriers

0 LQT1 · 24 unaffected

Functional studies

Publications with functional data

V418I is present in 24 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
-0.04	0.057	1	0.587	21

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. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source	Year	Carriers	Unaffected	LQT1	Other Disease
Literature, cohort, and gnomAD	–	24	24	0	–
Variant features alone	–	15	8	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 V418I.
Neighbour residue	Distance (Å)	Observed variants
418	0	V418I,
417	4	V417M,
419	4
416	5	V416M,
420	5	K420E, K420N, K420N,
415	7
421	7	K421N, K421N,
414	8
422	8	K422T, K422R,
413	8	K413R,
423	8
412	9	P412S,
424	9	K424T,
411	10
425	10	L425V,
410	11
426	11
409	11
427	11
408	12	P408A,
428	12	D428G,
407	13
429	13	N429S,
406	13
430	13
405	14
431	14	V431L, V431L,
404	14
432	14	T432I, T432A
403	15	H403P,
433	15	P433A,