GYS1 p.Ile583Ile

Variant names:

• chr19-48970605-T-T
• NM_002103.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-48970606--
• chr19-48970606-G-A
• chr19-48970606-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002103.5(GYS1):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GYS1 NM_002103.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• Publications: 0 publications found

Genes affected

GYS1 (HGNC:4706): (glycogen synthase 1) The protein encoded by this gene catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages. Mutations in this gene are associated with muscle glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

GYS1 Gene-Disease associations (from GenCC):

• glycogen storage disease due to muscle and heart glycogen synthase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002103.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS1	NM_002103.5	MANE Select	c.		exon_region	Exon 14 of 16	NP_002094.2
	GYS1	NM_001161587.2		c.		exon_region	Exon 13 of 15	NP_001155059.1	P13807-2
	GYS1	NR_027763.2		n.		exon_region	Exon 13 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS1	ENST00000323798.8	TSL:1 MANE Select	c.		exon_region	Exon 14 of 16	ENSP00000317904.3	P13807-1
	GYS1	ENST00000263276.6	TSL:1	c.		exon_region	Exon 13 of 15	ENSP00000263276.6	P13807-2
	GYS1	ENST00000960032.1		c.		exon_region	Exon 14 of 16	ENSP00000630091.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-49473862;