We estimate the penetrance of LQTS for KCNH2 P151fsX is %. This variant was found in a total of 29 carriers in 10 papers or gnomAD (version 4), 13 had LQTS. P151fsX is not present in gnomAD. P151fsX has not been functionally characterized. This residue is located in a None region for LQT2.

PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density (%)
None	None	None	None

PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 are considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected. Penetrance density is our previously published method to calculate the average LQTS probability density in a shell of residues surrounding a residue of interest (Kroncke et al. 2019).

PubMed ID	Year	Carriers	Unaffected	LQT2	Other Disease
24606995	2014	1	0	1
Japan Cohort	2020	1	0	1
Japan Cohort	2020	1	0	1
15840476	2005	1	0	1
24015048	2013	5	1	4
10973849	2000	1	0	1
15840476	2005	2	0	2
		2	0	2
16922724	2006	1	0	1
10862094		19	15	4
LITERATURE, COHORT, AND GNOMAD:	-	29	16	13	-
VARIANT FEATURES ALONE:	-	10	NA	NA	-

Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts. We do not distinguish here between multiple missense codons. Missense variants are combined across degenerate codon substitutions since codon-level data were not consistently available for curation.