Table 3.

Summary of likely pathogenic variants among sudden cardiac death victims with presumed acquired cardiac disease.

Mutated gene	Subject no	Decade of life, gender	Presumed etiology of LVH	Heart weight, g	Myocardial fibrosis at autopsy	Nucleotide change	Effect on protein	Predicted effect	NGS coverage	gnomAD > 10,000 Finnish controls MAF	SISu > 10,000 Finnish controls MAF	ACMG score16	ClinVar adjudication
ABCC9	1	60M	Hypertension	476	Moderate patchy	565C>T	Arg189Ter	Truncating	175	0.0011	0.0008	PVS1 + PM4 + PP3	N/A
ACTN2	2	50M	Hypertension	427	Scattered mild	26A>G	Gln9Arg	Missense	261	0.0002	0.0001	PS3 + PP2 + PP4 (DCM, HCM)	Conflicting
ANKRD1	3	50M	Hypertension	446	Scattered mild	197G>A	Arg66Gln	Missense	369	0.0015	0.0012	PS4 + PP3 + PP4 (DCM)	Conflicting
ANKRD1	4	70M	Obesity	440	Scattered mild	197G>A	Arg66Gln	Missense	353	0.0015	0.0012	PS4 + PP3 + PP4 (DCM)	Conflicting
ANKRD1	5	30M	Obesity	525	Moderate patchy	197G>A	Arg66Gln	Missense	160	0.0015	0.0012	PS4 + PP3 + PP4 (DCM)	Conflicting
CAV3	6	50M	Hypertension	463	Scattered mild	233C>T	Thr78Met	Missense	181	0.0032	0.0025	PS1 + PP3 + PP4 (LQTS)	Conflicting
CAV3	7	50M	Obesity	411	Scattered mild	233C>T	Thr78Met	Missense	46a	0.0032	0.0025	PS1 + PP3 + PP4 (LQTS)	Conflicting
DES	8	60M	Hypertension	476	Scattered mild	934G>A	Asp312Asn	Missense	248	Not detected	Not detected	PS3 + PM1 + PM2 + PP2 + PP3 + PP4 (DCM) + PP5	VUS
DSG2	9	80F	Hypertension	529	Moderate patchy	1174G>A	Val392Ile	Missense	58	0.0009	0.0009	PS4 + PP2 + PP3 + PP4 (ACM)	Conflicting
DSG2	10	70F	Hypertension	620	Some fibrosis	1174G>A	Val392Ile	Missense	119	0.0009	0.0009	PS4 + PP2 + PP3 + PP4 (ACM)	Conflicting
LMNA	11	50M	Hypertension	454	Moderate patchy	504G>C	Gln168His	Missense	77	Not detected	Not detected	PM1 + PM2 + PP2 + PP3	VUS
MYH6	8	60M	Hypertension	476	Scattered mild	346-2A>G		Affects canonical splicing	112	Not detected	Not detected	PVS1 + PM2	VUS
MYH6	12	50M	Obesity	673	Some fibrosis	3195G>C	Gln1065His	Missense	319	0.0017	0.0017	PS1 + PM1 + PP3 + PP4 (HCM)	Conflicting
MYH7	13	50M	Obesity	472	Moderate patchy	2945 T>C	Met982Thr	Missense	95	0.0005	0.0005	PS1 + PM1 + PP2 + PP3 + PP4 (HCM)	Benign
PKP2	14	50M	Obesity	651	Moderate patchy	1114G>C	Ala372Pro	Missense	23a	0.0023	0.0023	PM6 + PP2 + PP3 + PP4 (ACM)	Conflicting
TCAP	15	40M	Obesity	530	Some fibrosis	458G>A	Arg153His	Missense	131	0.0022	0.0019	PS1 + PP1 + PP2 + PP4 (HCM)	Conflicting

ACMG American college of molecular genetics, ACM arrhythmogenic cardiomyopathy, DCM dilated cardiomyopathy, HCM hypertrophic cardiomyopathy, LQTS long QT syndrome, LVH left ventricle hypertrophy, MAF minor allele frequency, NGS next generation sequencing, VUS variant of uncertain significance.

^aVerified by Sanger sequencing.