KCNQ1 Variant S373P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S373P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

49%

5/12 effective observations

Total carriers

2

1 LQT1 · 1 unaffected

Functional studies

1

Publications with functional data

S373P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-2.82 0.996 2 0.764 53

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
32893267 2020 1 None 1 None
19490272 2009 6 None 6 None
17470695 2007 7 None 7 None
17192539 2006 1 None 1 None
12566525 2003 1 None 1 None
10220144 1999 7 1 1 None
Literature, cohort, and gnomAD – 2 1 1 –
Variant features alone – 15 6 4 –

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

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 S373P.
Neighbour residue Distance (Å) Observed variants
373 0 S373P,
372 4
374 5 L374H, L374F,
376 5
370 5 A370V,
371 5 A371T,
525 5 A525T, A525V,
377 6
375 6
369 7
528 8
529 8
522 8 Y522S,
524 8 V524G,
378 9 A378T,
521 9
380 9 R380S, R380S, R380G,
368 10
526 10 K526Q, K526E,
523 11
367 11 Q367H, Q367H,
527 11
532 12
379 12 W379R, W379R, W379C, W379C, W379G
381 12 C381Y,
530 12
518 12 R518Q, R518G,
520 13 M520R,
531 14
533 14 R533W, R533Q,
517 14 I517T,
519 14 R519H, R519C,
365 14 N365H,
366 15 R366W, R366Q,