The NM_003494.4: c.107_108del p.(Lys36SerfsTer12) variant in DYSF, which is also known as NM_001130987.2: c.110_111del p.(Lys37SerfsTer12), is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 2/55, 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 four individuals with features consistent with LGMD (PMID: 19528035, 18853459; ClinVar SCV004229601.1 internal data communication), including in unknown phase with a pathogenic variant (NM_003494.4: c.2643+1G>A, 0.5 pts, ClinVar SCV004229601.1 internal data communication) (PM3_Supporting). This variant has been reported to co-segregate with autosomal recessive LGMD in two affected family members from two families (PMID: 18853459, 19528035; PP1_Moderate). In addition, at least one patient with this variant and a second presumed diagnostic DYSF variant displayed progressive limb girdle muscle weakness and severely reduced or absent dysferlin protein expression in skeletal muscle, which is highly specific for DYSF-related LGMD (PMID: 18853459, 17698709; PP4_Moderate, capped with PP1_Moderate). The filtering allele frequency of this variant in gnomAD v4.1.0 exomes is 0.000016374 (the lower threshold of the 95% CI of 11/1111948 European (non-Finnish) chromosomes), which is lower than the LGMD VCEP threshold (<0.0001) for PM2_Supporting, meeting 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 (LGMD VCEP specifications version 1.0.0; 07/29/2025): PVS1, PM3_Supporting, PP1_Moderate, PP4_Moderate, PM2_Supporting.