KCNQ1 Variant Y395C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 Y395C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

19%

2/12 effective observations

Total carriers

2

0 LQT1 · 2 unaffected

Functional studies

0

Publications with functional data

Y395C is present in 2 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 (%)
-6.58 1.0 -3 0.847 20

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 – 2 2 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 Y395C.
Neighbour residue Distance (Å) Observed variants
395 0 Y395C,
394 4 I394L,
396 4
393 5 K393N,
397 5 R397W, R397Q, R397G,
392 7 W392R, W392R, W392ins
398 7 K398R,
391 8 T391A, T391I,
399 8 A399S, A399V, A399G,
390 8
400 8
389 9 S389P,
401 9 R401W, R401Q,
388 10 D388H, D388N,
402 10
387 11 P387T,
403 11 H403P,
386 11 N386K, N386K,
404 11
385 12 E385K,
405 12
384 13
406 13
383 13
407 13
382 14
408 14 P408A,
381 14 C381Y,
409 14
380 15 R380S, R380S, R380G,
410 15