Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000070.3(CAPN3):c.717del (p.Phe239fs)

CA7511095

284807 (ClinVar)

Gene: CAPN3 (HGNC:825)

Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)

Inheritance Mode: Autosomal recessive inheritance

UUID: 27330316-f60e-491c-8a82-8a1f1bde9ac8

Approved on: 2026-04-29

Published on: 2026-05-07

HGVS expressions

NM_000070.3:c.717delT

NM_000070.3(CAPN3):c.717del (p.Phe239fs)

NM_000070.3:c.717del

NC_000015.10:g.42389012del

CM000677.2:g.42389012del

NC_000015.9:g.42681210del

CM000677.1:g.42681210del

NC_000015.8:g.40468502del

NG_008660.1:g.45910del

ENST00000349748.8:c.717del

ENST00000357568.8:c.717del

ENST00000397163.8:c.717del

ENST00000466369.5:n.1226del

ENST00000483208.5:n.948del

ENST00000495723.1:n.948del

ENST00000549793.5:n.948del

ENST00000638141.2:n.732del

ENST00000673705.1:c.70+4460del

ENST00000318023.11:c.717del

ENST00000349748.7:c.717del

ENST00000357568.7:c.717del

ENST00000397163.7:c.717del

NM_000070.2:c.717del

NM_024344.1:c.717del

NM_173087.1:c.717del

NM_024344.2:c.717del

NM_173087.2:c.717del

Pathogenic

PP4_Strong PM3 PM2_Supporting PVS1

PS4

Evidence Links 0

Expert Panel

Limb Girdle Muscular Dystrophy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CAPN3 Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Limb Girdle Muscular Dystrophy VCEP

The NM_000070.3: c.717del (p.Phe239LeufsTer14) variant in CAPN3 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 5/24, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been identified in a homozygous state in six patients with signs of LGMD (1.0 pt; PMID: 10330340, 18073330, 17236769; PM3). At least one of the patients had a clinical diagnosis of LGMD and absent calpain-3 protein expression, which is highly specific for CAPN3-related LGMD (PMID: 17236769; PP4_Strong). The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.1 is 0.00001 (6/1180006 European (non-Finnish) chromosomes), which is lower than the ClinGen LGMD VCEP threshold (<0.0001) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (specifications v2.0.0; 04/29/2026): PVS1, PM3, PP4_Strong, PM2_Supporting.

PP4_Strong

At least one of the patients had a clinical diagnosis of LGMD and absent calpain-3 protein expression, which is highly specific for CAPN3-related LGMD (PMID: 17236769; PP4_Strong).

PM3

This variant has been identified in a homozygous state in six patients with signs of LGMD (1.0 pt; PMID: 10330340, 18073330, 17236769; PM3).

PM2_Supporting

The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.1 is 0.00001 (6/1180006 European (non-Finnish) chromosomes), which is lower than the ClinGen LGMD VCEP threshold (<0.0001) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).

PVS1

The NM_000070.3: c.717del (p.Phe239LeufsTer14) variant in CAPN3 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 5/24 leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). SpliceAI: 0.00

PS4

PS4_Mod mentioned in ClinVar submission ?

Curation History

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