Functional evaluation of gene mutations in Long QT Syndrome: strength of evidence from in vitro assays for deciphering variants of uncertain significance

Table 1 Automated patch clamp technology enables the phenotyping of KCNQ1, KCNH2 and SCN5A variants to be performed in a high-throughput manner

Study:	Expression system:	Automated patch clamp platform:	No of variants studied:		Classification:
Study:	Expression system:	Automated patch clamp platform:	Homozygous state:	Heterozygous State:	P or LP:	B or LB:	GOF:	VUS:
*KCNQ1* [34]	CHO-K1	Syncropatch 768 PE - Recording at RT	78 (30 training + 48 test variants)	22	44	16	3	15
*KCNH2* [35]	HEK-293	Syncropatch 384 PE - Recording at ~ 25 °C	23	30	26^a	2^a	0^a	2^a
*SCN5A* [36]	HEK-293 T	Syncropatch 384 PE - Recording at RT	83 (73 previously unstudied)	N/A	54	17	0	12

P Pathogenic, LP Likely Pathogenic, B Benign, LB Likely Benign, GOF Gain of Function, VUS Variant of Uncertain Significance. KCNQ1 variant classification is inferred from in text information and data presented in Supplementary Tables S4a and S4b [34]. KCNH2 variant classification is as reported in [35]. ^a Indicates that pathogenicity was classified in the heterozygotic state to mimic the patient phenotype [35]. SCN5A variant classification is taken from Supplementary Table S1 [36]. The Syncropatch 384 and 768 PE automated patch clamp platforms are developed by Nanion Technologies

ISSN: 2056-7251