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 label mismatch: DYSF vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001130987.2(DYSF):c.2266C>T (p.Gln756Ter)

CA347208953

1433815 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: 71a57ffa-8ae3-48e6-bdc5-8b296b89d91c
Approved on: 2025-07-23
Published on: 2025-08-14

HGVS expressions

NM_001130987.2:c.2266C>T
NM_001130987.2(DYSF):c.2266C>T (p.Gln756Ter)
NC_000002.12:g.71561801C>T
CM000664.2:g.71561801C>T
NC_000002.11:g.71788931C>T
CM000664.1:g.71788931C>T
NC_000002.10:g.71642439C>T
NG_008694.1:g.113179C>T
ENST00000258104.8:c.2212C>T
ENST00000410020.8:c.2266C>T
ENST00000258104.7:c.2212C>T
ENST00000394120.6:c.2215C>T
ENST00000409366.5:c.2215C>T
ENST00000409582.7:c.2263C>T
ENST00000409651.5:c.2308C>T
ENST00000409744.5:c.2173C>T
ENST00000409762.5:c.2263C>T
ENST00000410020.7:c.2266C>T
ENST00000410041.1:c.2266C>T
ENST00000413539.6:c.2305C>T
ENST00000429174.6:c.2212C>T
NM_001130455.1:c.2215C>T
NM_001130976.1:c.2170C>T
NM_001130977.1:c.2170C>T
NM_001130978.1:c.2212C>T
NM_001130979.1:c.2305C>T
NM_001130980.1:c.2263C>T
NM_001130981.1:c.2263C>T
NM_001130982.1:c.2308C>T
NM_001130983.1:c.2215C>T
NM_001130984.1:c.2173C>T
NM_001130985.1:c.2266C>T
NM_001130986.1:c.2173C>T
NM_001130987.1:c.2266C>T
NM_003494.3:c.2212C>T
NM_001130455.2:c.2215C>T
NM_001130976.2:c.2170C>T
NM_001130977.2:c.2170C>T
NM_001130978.2:c.2212C>T
NM_001130979.2:c.2305C>T
NM_001130980.2:c.2263C>T
NM_001130981.2:c.2263C>T
NM_001130982.2:c.2308C>T
NM_001130983.2:c.2215C>T
NM_001130984.2:c.2173C>T
NM_001130985.2:c.2266C>T
NM_001130986.2:c.2173C>T
NM_003494.4:c.2212C>T
More

Pathogenic

Met criteria codes 3
PP4 PVS1 PM2_Supporting
Not Met criteria codes 1
PM3

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 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Limb Girdle Muscular Dystrophy VCEP
The NM_003494.4: c.2212C>T p.(Gln738Ter) variant in DYSF, which is also known as NM_001130987.2: c.2266C>T p.(Gln756Ter), is a nonsense variant predicted to cause a premature stop codon in exon 23/55, leading to nonsense mediated decay in a gene in which loss of function is a known mechanism of disease (PVS1). This variant has been reported in a homozygous state in an individual with known familial consanguinity who displayed features of LGMD including proximal muscle weakness (0.25 pts, PMID: 39548682, LOVD individual #00391981) (PP4; PM3_Supporting not met). The highest allele frequency for this variant is 0.0000008474 in the European (non-Finnish) population of gnomAD v4.1.0 (1/1180024 chromosomes), which is less than the LGMD VCEP threshold for PM2_Supporting (0.0001), 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; 07/23/2025): PVS1, PP4, PM2_Supporting.
Met criteria codes
PP4
This variant has been reported in a homozygous state in an individual who displayed features of LGMD including proximal muscle weakness (PMID: 39548682, LOVD individual #00391981) (PP4).
PVS1
The NM_003494.4: c.2212C>T p.(Gln738Ter) variant in DYSF, which is also known as NM_001130987.2: c.2266C>T p.(Gln756Ter), is a nonsense variant predicted to cause a premature stop codon in exon 23/55, leading to nonsense mediated decay in a gene in which loss of function is a known mechanism of disease (PVS1).
PM2_Supporting
The highest allele frequency for this variant is 0.0000008474 in the European (non-Finnish) population of gnomAD v4.1.0 (1/1180024 chromosomes), which is less than the LGMD VCEP threshold for PM2_Supporting (0.0001), meeting this criterion (PM2_Supporting).
Not Met criteria codes
PM3
This variant has been reported in a homozygous state in an individual with known familial consanguinity who displayed features of LGMD including proximal muscle weakness (0.25 pts, PMID: 39548682, LOVD individual #00391981) (PM3_Supporting not met). Additional individuals with this variant present in Dysferlin Registry, but details not requested given a Pathogenic classification reached.
Curation History
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