KCNQ1 Variant V648I

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V648I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

9/609 effective observations

Total carriers

599

7 LQT1 · 592 unaffected

Functional studies

Publications with functional data

V648I is present in 484 alleles in gnomAD. This residue resides in a Non_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

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
29197658	2018	7	None	7	None
22949429	2012	9	9	None	None
19841300	2009	9	9	None	None
Literature, cohort, and gnomAD	–	599	592	7	–
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 V648I.
Neighbour residue	Distance (Å)	Observed variants
648	0	V648I,
647	4
649	4	D649N, D649G,
646	5	G646S
650	5
645	7
651	7
644	8
652	8
643	8	G643S,
653	8	F653Y,
642	9
654	9
641	10	P641L,
655	10
640	11	Q640L,
656	11
639	11
657	11	N657S,
638	12
658	12	T658N,
637	13
659	13
636	13
660	13	P660S,
635	14	G635R, G635R,
661	14
634	14
662	14
633	15
663	15	E663K,