The NM_003494.4: c.3444_3445delTGinsAA p.(Tyr1148Ter) variant in DYSF, which is also known as NM_001130987.2: c.3498_3499delinsAA p.(Tyr1166Ter), is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 32/55, 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 10 unrelated individuals with LGMD (PMID: 195280, 27066573, 27602406, 30564623) including in a homozygous state in four patients, which includes a sibling pair, all without reported familial consanguinity (1.0 pt, PMID: 15469449, 27602406) and in unknown phase with a pathogenic variant in one patient (c.6124C>T p.(Arg2042Cys), 0.5 pts, PMID: 27602406). The variant was also identified in two affected siblings in a confirmed trans phase with a pathogenic variant (c.4886+1249G>T, 1.0 pt, PMID: 30564623) (PM3_Strong; PP1). At least one of these patients had a clinical diagnosis of LGMD and absent dysferlin protein expression, which is highly specific for DYSF-related LGMD (PMID: 27602406; PP4_Strong). While this variant is not called as an insertion-deletion in gnomAD v4.1.0, read data indicates the presence of both component single nucleotide variants in cis in multiple individuals. The frequency of one component variant, (c.3444T>A p.(Tyr1148Ter), is also below the LGMD VCEP threshold (≤0.0001) (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; 01/23/2026): PVS1, PM3_Strong, PP4_Strong, PP1, PM2_supporting.