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.258dup (p.Leu87fs)

CA7510881

284122 (ClinVar)

Gene: CAPN3 (HGNC:825)

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

Inheritance Mode: Autosomal recessive inheritance

UUID: 792ead27-5e82-4a70-8702-a85323b5b211

Approved on: 2026-02-18

Published on: 2026-04-09

HGVS expressions

NM_000070.3(CAPN3):c.258dup (p.Leu87fs)

NM_000070.3:c.258dup

NC_000015.10:g.42360063dup

CM000677.2:g.42360063dup

NC_000015.9:g.42652261dup

CM000677.1:g.42652261dup

NC_000015.8:g.40439553dup

NG_008660.1:g.16961dup

ENST00000349748.8:c.258dup

ENST00000357568.8:c.258dup

ENST00000397163.8:c.258dup

ENST00000466369.5:n.540+5610dup

ENST00000483208.5:n.540+5610dup

ENST00000495723.1:n.540+5610dup

ENST00000549793.5:n.540+5610dup

ENST00000318023.11:c.258dup

ENST00000349748.7:c.258dup

ENST00000357568.7:c.258dup

ENST00000397163.7:c.258dup

NM_000070.2:c.258dup

NM_024344.1:c.258dup

NM_173087.1:c.258dup

NM_024344.2:c.258dup

NM_173087.2:c.258dup

Pathogenic

PP4 PM3 PVS1

PM2

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.258dup p.(Leu87SerfsTer4) variant in CAPN3 is a frameshift variant expected to cause a premature stop codon in biologically relevant exon 1/24, 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 at least three individuals with a clinical diagnosis or suspicion of LGMD without reported familial consanguinity (1.0 pt; PMID: 16650086, 30564623; LOVD CAPN3_000380) (PM3, PP4). The highest frequency of this variant in gnomAD v4.1.0 is 0.0002135 in the African/African American population (16/74948 alleles), which is greater than the LGMD VCEP threshold of 0.0001 (PM2_Supporting not met). 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, PM3, PP4.

PP4

This variant has been identified in a homozygous state in at least three individuals with a clinical diagnosis or suspicion of LGMD without reported familial consanguinity (1.0 pt; PMID: 16650086, 30564623; LOVD CAPN3_000380) (PM3, PP4).

PM3

PVS1

PM2

The highest frequency of this variant in gnomAD v4.1.0 is 0.0002135 in the African/African American population (16/74948 alleles), which is greater than the LGMD VCEP threshold of 0.0001 (PM2_Supporting not met).

Curation History

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