Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: DYSF CSPEC Genes: [ 'DYSF' ] * Message MONDOs: MONDO:0016971 CSPEC MONDO: [ 'MONDO:0015152' ]
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001130987.2(DYSF):c.3381_3382del (p.Phe1128fs)

CA222154

94303 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: limb-girdle muscular dystrophy (MONDO:0016971)
Inheritance Mode: Autosomal recessive inheritance
UUID: f53de391-e73a-469c-928e-cec5a6ce81e4
Approved on: 2026-02-10
Published on: 2026-02-17

HGVS expressions

NM_001130987.2(DYSF):c.3381_3382del (p.Phe1128fs)
NM_001130987.2:c.3381_3382del
NC_000002.12:g.71574350_71574351del
CM000664.2:g.71574350_71574351del
NC_000002.11:g.71801480_71801481del
CM000664.1:g.71801480_71801481del
NC_000002.10:g.71654988_71654989del
NG_008694.1:g.125728_125729del
ENST00000698057.1:c.753_754del
ENST00000258104.8:c.3327_3328del
ENST00000410020.8:c.3381_3382del
ENST00000258104.7:c.3327_3328del
ENST00000394120.6:c.3330_3331del
ENST00000409366.5:c.3330_3331del
ENST00000409582.7:c.3378_3379del
ENST00000409651.5:c.3423_3424del
ENST00000409744.5:c.3288_3289del
ENST00000409762.5:c.3378_3379del
ENST00000410020.7:c.3381_3382del
ENST00000410041.1:c.3381_3382del
ENST00000413539.6:c.3420_3421del
ENST00000429174.6:c.3327_3328del
NM_001130455.1:c.3330_3331del
NM_001130976.1:c.3285_3286del
NM_001130977.1:c.3285_3286del
NM_001130978.1:c.3327_3328del
NM_001130979.1:c.3420_3421del
NM_001130980.1:c.3378_3379del
NM_001130981.1:c.3378_3379del
NM_001130982.1:c.3423_3424del
NM_001130983.1:c.3330_3331del
NM_001130984.1:c.3288_3289del
NM_001130985.1:c.3381_3382del
NM_001130986.1:c.3288_3289del
NM_001130987.1:c.3381_3382del
NM_003494.3:c.3327_3328del
NM_001130455.2:c.3330_3331del
NM_001130976.2:c.3285_3286del
NM_001130977.2:c.3285_3286del
NM_001130978.2:c.3327_3328del
NM_001130979.2:c.3420_3421del
NM_001130980.2:c.3378_3379del
NM_001130981.2:c.3378_3379del
NM_001130982.2:c.3423_3424del
NM_001130983.2:c.3330_3331del
NM_001130984.2:c.3288_3289del
NM_001130985.2:c.3381_3382del
NM_001130986.2:c.3288_3289del
NM_003494.4:c.3327_3328del
More

Pathogenic

Met criteria codes 4
PVS1 PP4 PM2_Supporting PM3_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DYSF 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_003494.4: c.3327_3328del p.(Phe1110CysfsTer3) variant in DYSF, which is also known as NM_001130987.2: c.3381_3382del p.(Phe1128CysfsTer3), is a frameshift variant that is predicted to result in a premature stop codon in exon 30/55, leading to nonsense mediated decay in a gene in which loss of function is an established mechanism of disease (PVS1). This variant has been reported in at least two unrelated patients with clinical signs of LGMD (PMID: 35723113, 34559919), including in unconfirmed phase with a pathogenic variant (NM_003494.4: c.965T>C p.(Leu322Pro), PMID: 34559919, 0.5 pts) (PM3_Supporting). At least one patient with this variant and a second presumed diagnostic DYSF variant displayed progressive limb girdle muscle weakness (PMID: 34559919; PP4). This variant is also 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 LGMD VCEP specifications version 2.0.0; 02/10/2026): PVS1, PM3_Supporting, PP4, PM2_Supporting.
Met criteria codes
PVS1
The NM_003494.4: c.3327_3328del p.(Phe1110CysfsTer3) variant in DYSF, which is also known as NM_001130987.2: c.3381_3382del p.(Phe1128CysfsTer3), is a frameshift variant that is predicted to result in a premature stop codon in exon 30/55, leading to nonsense mediated decay in a gene in which loss of function is an established mechanism of disease (PVS1). SpliceAI 0.01
PP4
At least one patient with this variant and a second presumed diagnostic DYSF variant displayed progressive limb girdle muscle weakness (PMID: 34559919; PP4).
PM2_Supporting
Variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PM3_Supporting
This variant has been reported in at least two unrelated patients with clinical signs of LGMD (PMID: 35723113, 34559919), including in unconfirmed phase with a pathogenic variant (NM_003494.4: c.965T>C p.(Leu322Pro), PMID: 34559919, 0.5 pts) (PM3_Supporting).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
ClinGen Terms of Use.
¤ Powered by BCM's Genboree.