Submissions for variant NM_000151.4(G6PC1):c.150_151del (p.Trp50fs)

dbSNP: rs1057516674

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409261	SCV000486049	likely pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2016-03-22	criteria provided, single submitter	clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000409261	SCV000891162	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2019-03-02	criteria provided, single submitter	clinical testing	The observed variant NM_000151.3:g.230_231delGT/p.Trp50CysfsTer10 is a two base pair deletion in exon 1 of the G6PC gene. It has not been reported in the 1000 Genomes and ExAC databases. It has been reported as a common mutation in Indian patients with glycogen storage disease type Ia by Meaney.C et al (2001). The in silico prediction of this variant is disease causing by MutationTaster2. The reference codon is conserved across species.
Lifecell International Pvt. Ltd	RCV000409261	SCV003924084	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA		criteria provided, single submitter	clinical testing	A Homozygote Frameshift variant c.150_151delGT in Exon 1 of the G6PC1 gene that results in the amino acid substitution p.Trp50fs*10 was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic/Likely Pathogenic [Variation ID: 370671]. The observed variation has been previously reported in Glycogen storage disorder type I patients (Meaney C, et.al, 2001). For these reasons, this variant has been classified as Pathogenic.
Invitae	RCV000409261	SCV004297778	pathogenic	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	2023-02-16	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 370671). This sequence change creates a premature translational stop signal (p.Trp50Cysfs*10) in the G6PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type Ia (PMID: 11596659). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.