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.1743_1744del (p.Glu582fs)

CA10604416

283179 (ClinVar)

Gene: CAPN3 (HGNC:825)

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

Inheritance Mode: Autosomal recessive inheritance

UUID: 52524095-2571-4b87-98cc-3e7ef324e320

Approved on: 2026-02-18

Published on: 2026-04-09

HGVS expressions

NM_000070.3(CAPN3):c.1743_1744del (p.Glu582fs)

NM_000070.3:c.1743_1744del

NC_000015.10:g.42403000_42403001del

CM000677.2:g.42403000_42403001del

NC_000015.9:g.42695198_42695199del

CM000677.1:g.42695198_42695199del

NC_000015.8:g.40482490_40482491del

NG_008660.1:g.59898_59899del

ENST00000349748.8:c.1599_1600del

ENST00000357568.8:c.1743_1744del

ENST00000397163.8:c.1743_1744del

ENST00000466369.5:n.2252_2253del

ENST00000483208.5:n.2632_2633del

ENST00000495723.1:n.2632_2633del

ENST00000549793.5:n.1974_1975del

ENST00000638141.2:n.1614_1615del

ENST00000673646.1:c.207_208del

ENST00000673705.1:c.309+3348_309+3349del

ENST00000673813.1:n.580+85_580+86del

ENST00000318023.11:c.1599_1600del

ENST00000349748.7:c.1599_1600del

ENST00000357568.7:c.1743_1744del

ENST00000397163.7:c.1743_1744del

ENST00000397200.8:c.207_208del

ENST00000567071.5:c.202_203del

ENST00000569827.5:c.207_208del

NM_000070.2:c.1743_1744del

NM_024344.1:c.1743_1744del

NM_173087.1:c.1599_1600del

NM_173088.1:c.207_208del

NM_024344.2:c.1743_1744del

NM_173087.2:c.1599_1600del

NM_173088.2:c.207_208del

Pathogenic

PP4 PM2_Supporting PVS1

PM3

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.1743_1744del p.(Glu582GlyfsTer3) variant in CAPN3 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 13/24, 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 at least two patients with features consistent with LGMD (PMID: 30564623, 15689361, 10330340), at least one of whom had a second presumed diagnostic CAPN3 variant as well as a clinical suspicion of LGMD (PMID: 15689361, LOVD Individual #00214348; PP4). This variant is absent from gnomAD v4.1.0 (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 Limb Girdle Muscular Dystrophy Expert Panel (specifications version 2.0.0; 02/18/2026): PVS1, PM2_Supporting, PP4.

PP4

At least one individual with this variant and a second presumed diagnostic CAPN3 variant displayed progressive limb girdle muscle weakness or had a clinical suspicion of LGMD (PMID: 15689361, LOVD Individual #00214348; PP4).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PVS1

PM3

This variant has been identified in at least two patients with features consistent with LGMD (PMID: 30564623, 15689361, 10330340).

Curation History

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