Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand

Table 1 Genetic variants associated with glycogen storage disease

Patient number	Gene	WES	Variant	Amino acid	Exon/Intron	Zygosity	Inheriting parent of allele1	Transcript	hg19 coordinate	Ref.
GSD Ia
5	G6PC	Duo	c.648G>T	p.Leu216Leu	Exon 5	Homozygous or Hemizygous2	Mother	NM_000151.4	chr17:41063017 G>T	[21]
GSD III
3	AGL	Trio	c.2578delG	p.Val860LeufsTer8	Exon 20	Homozygous	Father and mother	NM_000642.3	chr1:100350156 delG	Clinvar RCV003060970.13
4	AGL	Singleton	c.1611+1G>C	N/A	Intron 12	Heterozygous	Unknown	NM_000642.3	chr1:100343385 G>C	Novel4
			c.1735G>A	p.Glu579Lys	Exon 13	Heterozygous	Unknown	NM_000642.3	chr1:100345602 G>A	Novel4
6	AGL	Trio	c.1735+1G>T	N/A	Intron 13	Homozygous	Father and mother	NM_000642.3	chr1:100345603 G>T	[22]
GSD VI
2	PYGL	Trio	c.514C>T	p.Arg172Ter	Exon 4	Heterozygous	Father	NM_002863.5	chr14:51398405 G>A	[9]
			c.2467C>T	p.Gln823Ter	Exon 20	Heterozygous	Mother	NM_002863.5	chr14:51372187 G>A	[9]
7	PYGL	Singleton	c.2467C>T	p.Gln823Ter	Exon 20	Heterozygous	Unknown	NM_002863.5	chr14:51372187 G>A	[9]
			c.932G>A	p.Arg311His	Exon 8	Heterozygous	Unknown	NM_002863.5	chr14:51383747 C>T	[23]
8	PYGL	Trio	c.1726C>T	p.Arg576Ter	Exon 14	Heterozygous	Father	NM_002863.5	chr14:51378916 G>A	[24]5
			c.2467C>T	p.Gln823Ter	Exon 20	Heterozygous	Mother	NM_002863.5	chr14:51372187 G>A	[9]
GSD IX
1	PHKA2	Trio	c.2746C>T	p.Arg916Trp	Exon 25	hemizygous	Mother	NM_000292.3	chrX:18924673 G>A	[25]

¹Biallelic variants identified by singleton exome sequencing analysis will be reported as "parental origin unknown.

²The duo exome sequencing performed on patient #5 and the mother, due to the unavailability of the father's DNA, has shown that the zygosity of the G6PC:c.648G>T variant cannot be distinguished between homozygous (inherited from both parents) and hemizygous (inherited from the mother only).

³Although no individuals with AGL-related conditions have been previously reported in the literature with this variant, ClinVar classifies the AGL:c.2578delG variant as pathogenic (Accession: RCV003060970.1) based on a submission ID: SCV003456543.1 by Invitae.

⁴Novel: a novel variant means that it is not present in the public database including literatures in pubmed, GRCh38/hg38 or GRCh37/hg19 gnomAD, and Clinvar databases.

⁵No reports of the PYGL:c.932G>A (p.Arg311His) variant exist in patients with glycogen storage disease type VI. However, the literature on colorectal carcinoma documents its presence[24].

WES: Whole-exome sequencing; GSD: Glycogen storage diseases.