. Author manuscript; available in PMC: 2022 Aug 13.

Published in final edited form as: Circ Genom Precis Med. 2021 Aug 13;14(4):e003200. doi: 10.1161/CIRCGEN.120.003200

Table 3:

Comparison of the prevalence of incidental LP/P variants and VUS associated with inherited cardiac channelopathies and cardiomyopathies

Disease	SNR Pathogenic: Population	Incidental Variant Prevalence vs Disease Prevalence^*		References
		Incidental LP/P: Prevalence	Incidental VUS: Prevalence
Hypertrophic cardiomyopathy	10:1	2.5-fold	34-fold	^25–29
Arrhythmogenic right ventricular cardiomyopathy	3.8:1	20-fold	700-fold	^{30, 31}
Dilated cardiomyopathy	2.14:1	N/A	N/A	^32–36
Catecholaminergic polymorphic ventricular tachycardia	8.3:1	20-fold	900-fold	^37–39
Long QT syndrome	7.5:1	10-fold ^† 24-fold^‡	220-fold 740-fold^‡	^{24, 40, 41}
Brugada syndrome	4.2:1	6-fold^§	126-fold^§	⁴²

Disease-specific SNR calculations based on the following disease-associated genes:

HCM: MYH7, MYL3, MYL3, MYBPC3, TNNT2, TNNTI3, TNNC1, TPM1, ACTC

ARVC: PKP2, DSP, DSG2, DSC2, JUP, TMEM43, TGFB3, PKP4, PERP

DCM: TTNtvs

CPVT: RYR2, CASQ2

LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, KCNJ5, CALM1, CALM2, CALM3, TRDN

Brugada Syndrome: SCN5A

Calculation based on presumption that all individuals with disease are genotype positive.

^†

Only ACMG-designated actionable genes associated with LQTS (KCNQ1, KCNH2, and SCN5A).

^‡

All LQTS-associated genes.

^§

Based on SCN5A. N/A, not available.