Table 3.

Genetic variants identified in known short stature genes in the 6Ψ subjects.

Pt	Age (years)	Height SDS	IGF-1 SDS	Gene transcript	Translation	SIFT score	Polyphen	CADD score	ACMG/AMP classification
1	3.8	−3.6	−2.0	No deleterious variants detected	N/A	N/A	N/A	N/A	N/A
2	3.7	−4.2	−2.5	ACAN Het c.1223A>G, p.Q532H	Missense	Damaging	Probably damaging	23.7	Uncertain significance
3	2.6	−3.8	−2.3	No DNA available	N/A	N/A	N/A	N/A	N/A
4	2.8	−3.1	−2.5	OBSL1 Het c.2671A>G, p.T891A	Missense	Damaging	Probably damaging	26.8	Uncertain significance
				CBL Het c.125_127dupACC, p.H42dup	In-frame	NK	NK	12.6	Likely benign
5	5.7	−4.5	−2.5	OBSL1 Het c.2671A>G, p.T891A	Missense	Damaging	Probably damaging	26.8	Uncertain significance
6	1.2	−4.4	−2.2	IGF1R Het c.109_123dupATCGACATCCGCAAC, p.I37_N41dup	In-frame	NK	NK	NK	Uncertain significance
7	7.0	−4.2	−2.5	CBL Het c.2216C>T, p.S739F	Missense	Damaging	Benign	23.1	Uncertain significance
8	5.7	−3.0	−2.9	ACAN Het c.1596G>C, p.R132C	Missense	Damaging	Probably damaging	27.9	Uncertain significance
9	4.3	−4.1	−4.0	CUL7 Het c.464G>A, p.G155E c.620G>A, p.G207E	Missense	Damaging	Probably damaging	26.9	Uncertain significance
10	2.5	−4.4	NK	IGFALS Het c.544C>A, p.L220M c.658C>A, p.L182M	Missense	Damaging	Probably damaging	23.5	Uncertain significance
11	5.7	−4.7	−3.1	No deleterious variants detected	N/A	N/A	N/A	N/A	N/A
12	9.9	−5.1	−2.1	No deleterious variants detected	N/A	N/A	N/A	N/A	N/A

Patients 1–4 are the 6Ψ patients analysed for WT-GHR and 6Ψ-GHR transcript ratios (Table 2).

ACMG/AMP classification, classification as per the American College of Medical Genetics and Genomics and the Association for Molecular Pathology’s standards and guidelines for the interpretation of sequence variants; c., coding DNA sequence where nucleotide 1 is the A of the ATG-translation initiation codon (NCBI reference sequences: for ACAN, NM_013227.2; for OBSL1, NM_015311.2; for CBL, NM_005188.3; for IGF1R, NM_000875.3; for CUL7, NM_001168370.1 and for IGFALS, NM_004970.2); CADD, combined annotation dependent depletion; Ht, height; N/A, not applicable; NK, not known; Pt, patient (30).