KCNQ1 Variant N657S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 N657S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

1/30 effective observations

Total carriers

0 LQT1 · 20 unaffected

Functional studies

Publications with functional data

N657S is present in 20 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
0.06	0.002	1	0.424	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
Literature, cohort, and gnomAD	–	20	20	0	–
Variant features alone	–	15	9	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 N657S.
Neighbour residue	Distance (Å)	Observed variants
657	0	N657S,
656	4
658	4	T658N,
655	5
659	5
654	7
660	7	P660S,
653	8	F653Y,
661	8
652	8
662	8
651	9
663	9	E663K,
650	10
664	10
649	11	D649N, D649G,
665	11
648	11	V648I,
666	11
647	12
667	12	V667M,
646	13	G646S
668	13
645	13
669	13	R669S, R669S, R669T,
644	14
670	14	R670K,
643	14	G643S,
671	14	G671S,
642	15
672	15