Table 1.

Molecular findings in individuals with heterozygous missense SEPHS1 variants

	Individual 1	Individual 2	Individual 3	Individual 4	Individual 5	Individual 6	Individual 7	Individual 8	Individual 9
SEPHS1 variant (NM_012247.4)	c.1111C>T	c.1111C>T	c.1111C>T	c.1112G>A	c.1112G>A	c.1112G>A	c.1111C>G	c.1111C>G	c.1054T>G
Exon	exon 9	exon 9	exon 9	exon 9	exon 9	exon 9	exon 9	exon 9	exon 9
Protein	p.Arg371Trp	p.Arg371Trp	p.Arg371Trp	p.Arg371Gln	p.Arg371Gln	p.Arg371Gln	p.Arg371Gly	p.Arg371Gly	p.Trp352Gly
Inheritance	de novo	de novo	unknown	de novo	de novo	de novo	de novo	de novo	de novo
PROVEAN (cutoff 2.5)	−3.75	−3.75	−3.75	−1.15	−1.15	−1.15	−3.65	−3.65	−10.49
GnomAD frequency	0	0	0	0	0	0	0	0	0
Reported CNV and SNVs	none reported	none reported	CMA: gain of chr13q14.1 (VUS, unknown inheritance)a	none reported	none reported	CMA: gain of chr3p25.3 (VUS, maternally inherited)a	de novo VUS in SRCAP, NM_006662.2: c.3833C>A (p.Ser1278∗)29	none reported	heteroplasmic variant in MT-TL2; heterozygous VUS RAPSNa
ACMG criteria applied33	internal criteria, PM2, PP3	internal criteria, PM2, PP3	internal criteria, PM2, PP3	internal criteria, PS2, PM2, BP4	internal criteria, PS2, PM2, BP4	internal criteria, PS2, PM2, BP4	internal criteria, PM2, PP3	internal criteria, PM2, PP3	PS2, PS3, PM2, PP3
ACMG Class	PATH	PATH	PATH	PATH	PATH	PATH	PATH	PATH	PATH
ClinVar accession	SCV002103293 .1	SCV002103293.1	SCV002103293.1	SCV002103295.1	SCV002103295.1	SCV002103295.1	SCV002103294.2	SCV002103294.2	SCV002103296.1

CMA, chromosomal microarray

^aNo HGVS notation available