Table 3.

Details of homozygous variants identified in the Egypt HCM cohort (n = 514) compared to Egypt controls (n = 400)

Gene	Variant type	cDNA variant	Protein variant	gnomAD FAFpopmax	Control hom freq (count)	Control het freq (count)	HCM hom case freq (count)	HCM het case freq (count)
Sufficiently rare variants (gnomAD FAFpopmax ≤ 4 × 10−5) to cause monoallelic HCM
MYH7	Missense	c.5122G > A	p.Glu1708Lys	0	0%	0%	0.19% (1)	0%
	Missense	c.4258C > T	p.Arg1420Trp	3.0 × 10−6	0%	0%	0.19% (1)	0.39% (2)
	Missense	c.3622G > C	p.Asp1208His	0	0%	0%	0.19% (1)	0.58% (3)
	Missense	c.1064C > T	p.Ala355Val	0	0%	0%	0.19% (1)	0%
	Missense	c.925G > A	p.Asp309Asn	1.1 × 10−5	0%	0%	0.19% (1)	0.78% (4)
	Frameshifta	c.5769delG	p.Ser1924AlafsTer9	0	0%	0%	0.19% (1)	3.11% (16)
MYBPC3	Missense	c.2908C > T	p.Arg970Trp	0	0%	0.25% (1)	0.19% (1)	0.39% (2)
	Missense	c.2458C > G	p.Arg820Gly	0	0%	0%	0.19% (1)	0%
	Inframe Deletion	c.2441_2443delAGA	p.Lys814del	0	0%	0%	0.19% (1)	0%
	Nonsense	c.1558G > T	p.Glu520Ter	0	0%	0%	0.19% (1)	0%
	Splice acceptor	c.1227-2A > G		0	0%	0%	0.19% (1)	0.19% (1)
MYL2	Missense	c.278C > T	p.Ala93Val	0	0%	0%	0.19% (1)	0.78% (4)
MYL3	Missense	c.508G > C	p.Glu170Gln	0	0%	0%	0.58% (3)	0.58% (3)
TNNI3	Missense	c.485G > T	p.Arg162Leu	0	0%	0%	0.19% (1)	0%
CSRP3	Splice acceptor	c.415-1G > C		0	0%	0%	0.19% (1)	0%
	Splice donor	c.414 + 1G > T		0	0%	0.25% (1)	0.58% (3)	0.19% (1)
	Missense	c.365G > A	p.Arg122Gln	2.9 × 10−6	0%	0%	0.19% (1)	0.58% (3)
Sufficiently rare variants (gnomAD FAFpopmax ≤ 0.00126) to cause biallelic HCM
MYBPC3	Missense	c.3676C > T	p.Arg1226Cys	6.4 × 10−5	0%	0%	0.19% (1)	0%
	Missense	c.2618C > A	p.Pro873His	9.3 × 10−5	0%	0%	0.19% (1)	0%
	Missense	c.1321G > A	p.Glu441Lys	2.0 × 10−4	0%	2.0% (8)	0.39% (2)	4.3% (22)
MYL3	Missense	c.530A > G	p.Glu177Gly	4.4 × 10−5	0%	0.75% (3)	0.78% (4)	0.19% (1)
	Missense	c.170C > A	p.Ala57Asp	4.0 × 10−4	0%	0%	0.39% (2)	0.19% (1)
JPH2	Missense	c.572C > G	p.Pro191Argb	2.0 × 10−4	0%	0.25% (1)	0.19% (1)	0.19% (1)

Summary of Egyptian variants that are sufficiently rare (gnomAD FAF_popmax ≤ 4 × 10⁻⁵) to cause monoallelic disease and additional variants that are sufficiently rare (gnomAD FAF_popmax ≤ 0.00126) to cause biallelic disease are also shown.

^aThe MYH7 variant c.5769delG was caused by a nucleotide deletion that was predicted to ultimately give rise to a near full-length protein (i.e. only four AAs shorter than the wild type). The control frequency represents heterozygous counts (no homozygous variants were identified).

^bThis variant is unlikely to be pathogenic as it cooccurred with the pathogenic MYH7 variant p.Arg870His in the HCM patient (also, its allele frequency in gnomAD-Ashkenazi Jewish population is 0.007215).