Table 4.

A summary of the analysis of the splice site, frameshift and no-stop mutations

HGD exon	Short name	Nucleotide change	Protein change	CrypSkip prediction	BDGP splice sites prediction	Net2Gene splice sites prediction	Mutalyzer protein effect prediction	Effect
01i	IVS1-1G>A	c.16-1G>A	p.(Tyr6_Gln29del)	0.16 exon skipping strongly favoured	1 alternative acceptor site	No acceptable acceptor sites above threshold
3	S59fs	c.175delA	p.Ser59Alafsx52	–	–	–	Severely truncated protein 52 novel amino acids	Frameshift
5	IVS5+1G>T	c.342+1G>T	Uncertain (p.Leu95_Ser114del)*	0.42 cryptic splice site activation	2 alternative donor sites	2 alternative donor sites	No change in protein (if exon is skipped deletion of 20 amino acids)	Aberrant splicing
7	IVS7+2T>C	c.469+2T>C	p.Arg154SerfsX22	0.01 exon skipping strongly favoured	No alternative donor splice sites	No alternative donor splice sites	No change in protein	Exon skipping aberrant splicing
8	IVS8-1G>T (V157fs)	c.470-1_494del25	p.Val157Glufsx11 or if exon skipped p.Pro 158Thr fsx25	0.12 exon skipping strongly favoured	Acceptor splice site is abolished by the deletion	One alternative acceptor site	If skipped, a severely truncated protein with novel 10 residues + stop or a truncated protein with novel 24 residues + stop	Exon skip and frameshift
10	D226PfsX7	c.664_674dupGCCAATCCTCG	p.(Asp226Profs*7)	–	–	–	Severely truncated protein 7 novel amino acids	Frameshift
14	K431fs	c.1282-1292del11	p.Lys431Hisfsx52	–	–	–	Truncated protein with novel 10 residues + stop	Deletion causing frameshift
14	X446ext	c.1336G>C	p.X446ArgxtX24	–	–	–	Extended protein with additional 24 residues + stop	Extension

DNA variant numbering is based on cDNA (NM_000187.3), +1 corresponding to the A of the ATG. Protein effect numbering is based on NP_000178.2