VCV000162662.5 - ClinVar

NM_004130.4(GYG1):c.970C>T (p.Arg324Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic

3 out of 4 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004130.4(GYG1):c.970C>T (p.Arg324Ter)

Variation ID: 162662 Accession: VCV000162662.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q24 3: 149026850 (GRCh38) [ NCBI UCSC ] 3: 148744637 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 19, 2017	Feb 1, 2026	Oct 23, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_004130.4:c.970C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004121.2:p.Arg324Ter	nonsense
NM_001184720.2:c.919C>T	NP_001171649.1:p.Arg307Ter	nonsense
NM_001184721.2:c.699C>T	NP_001171650.1:p.Asn233=	synonymous
NC_000003.12:g.149026850C>T
NC_000003.11:g.148744637C>T
NG_027677.1:g.40443C>T

... more HGVS ... less HGVS

Protein change

R324*, R307*

Other names

Canonical SPDI

NC_000003.12:149026849:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00002

Links

ClinGen: CA175126 OMIM: 603942.0004 dbSNP: rs727502869 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GYG1		-	-	GRCh38 GRCh37	347	390

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Polyglucosan body myopathy type 2	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Oct 23, 2025	RCV000150099.7
Glycogen storage disease XV Polyglucosan body myopathy type 2	Likely pathogenic (1)	criteria provided, single submitter	Mar 9, 2022	RCV002498688.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Oct 23, 2025) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Polyglucosan body myopathy type 2	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV007336240.1 First in ClinVar: Feb 01, 2026 Last updated: Feb 01, 2026	Publications: PubMed (1) PubMed: 25272951 Comment: show Variant summary: GYG1 c.970C>T (p.Arg324X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 251356 control chromosomes. c.970C>T has been observed at a compound heterozygous state along with a second pathogenic variant in at-least one individual affected with Polyglucosan Body Myopathy Type 2 (example, Malfatti_2014). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in significantly reduced GYG1 levels and impaired elongation of the glycogen polymer of the residual truncated GYG1 (Malfatti_2014). The following publication has been ascertained in the context of this evaluation (PMID: 25272951). ClinVar contains an entry for this variant (Variation ID: 162662). Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Mar 09, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease XV Polyglucosan body myopathy type 2	Fulgent Genetics, Fulgent Genetics Accession: SCV002810964.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely pathogenic (Jul 30, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Polyglucosan body myopathy type 2 (Autosomal recessive inheritance)	Kariminejad - Najmabadi Pathology & Genetics Center Accession: SCV006074981.1 First in ClinVar: May 15, 2025 Last updated: May 15, 2025	Comment: show PM2,PVS1_mo,PM3_mo (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Dec 01, 2014) N Not contributing to aggregate classification	no assertion criteria provided	POLYGLUCOSAN BODY MYOPATHY 2	OMIM Accession: SCV000196923.3 First in ClinVar: Feb 02, 2015 Last updated: Apr 06, 2024	Publications: PubMed (1) PubMed: 25272951 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In a woman with onset of polyglucosan body myopathy-2 (PGBM2; 616199) at age 49 years, Malfatti et al. (2014) identified compound heterozygous mutations in the … (more) In a woman with onset of polyglucosan body myopathy-2 (PGBM2; 616199) at age 49 years, Malfatti et al. (2014) identified compound heterozygous mutations in the GYG1 gene: a c.970C-T transition in exon 8, resulting in an arg324-to-ter (R324X) substitution, and a splice site mutation resulting in a truncated protein (Asp3GlufsTer4; 603942.0003). (less)

Comment:

Variant summary: GYG1 c.970C>T (p.Arg324X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 251356 control chromosomes. c.970C>T has been observed at a compound heterozygous state along with a second pathogenic variant in at-least one individual affected with Polyglucosan Body Myopathy Type 2 (example, Malfatti_2014). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in significantly reduced GYG1 levels and impaired elongation of the glycogen polymer of the residual truncated GYG1 (Malfatti_2014). The following publication has been ascertained in the context of this evaluation (PMID: 25272951). ClinVar contains an entry for this variant (Variation ID: 162662). Based on the evidence outlined above, the variant was classified as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A new muscle glycogen storage disease associated with glycogenin-1 deficiency.	Malfatti E	Annals of neurology	2014	PMID: 25272951

Text-mined citations for rs727502869 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 01, 2026