KCNQ1 Variant P99R

Summary of observed carriers, functional annotations, and structural context for KCNQ1 P99R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

6%

1/23 effective observations

Total carriers

13

0 LQT1 · 13 unaffected

Functional studies

0

Publications with functional data

P99R is present in 13 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 (%)
-1.48 0.242 1 0.861 3

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
24631775 2014 1 None None None
Literature, cohort, and gnomAD – 13 13 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 P99R.
Neighbour residue Distance (Å) Observed variants
99 0 P99R, P99Q,
98 4 R98H,
100 4
97 5
101 5
96 7 T96R,
102 7
95 8 S95G,
103 8
94 8
104 8 T104A, T104I,
93 9 I93V,
105 9
92 10 S92P,
106 10
91 11 V91L
107 11 Q107H, Q107H,
90 11
108 11 G108S,
89 12 P89T, P89L,
109 12 R109C, R109L,
88 13 D88E, D88E,
110 13 V110I,
87 13
111 13 Y111C,
86 14 S86R, S86R, S86R,
112 14
85 14
113 14
84 15
114 15