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
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001130987.2(DYSF):c.2344G>T (p.Glu782Ter)

CA10606093

288442 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: a165712f-7feb-401b-a6a4-afc99f0e5ff0
Approved on: 2026-01-23
Published on: 2026-02-17

HGVS expressions

NM_001130987.2:c.2344G>T
NM_001130987.2(DYSF):c.2344G>T (p.Glu782Ter)
NC_000002.12:g.71561879G>T
CM000664.2:g.71561879G>T
NC_000002.11:g.71789009G>T
CM000664.1:g.71789009G>T
NC_000002.10:g.71642517G>T
NG_008694.1:g.113257G>T
ENST00000258104.8:c.2290G>T
ENST00000410020.8:c.2344G>T
ENST00000258104.7:c.2290G>T
ENST00000394120.6:c.2293G>T
ENST00000409366.5:c.2293G>T
ENST00000409582.7:c.2341G>T
ENST00000409651.5:c.2386G>T
ENST00000409744.5:c.2251G>T
ENST00000409762.5:c.2341G>T
ENST00000410020.7:c.2344G>T
ENST00000410041.1:c.2344G>T
ENST00000413539.6:c.2383G>T
ENST00000429174.6:c.2290G>T
NM_001130455.1:c.2293G>T
NM_001130976.1:c.2248G>T
NM_001130977.1:c.2248G>T
NM_001130978.1:c.2290G>T
NM_001130979.1:c.2383G>T
NM_001130980.1:c.2341G>T
NM_001130981.1:c.2341G>T
NM_001130982.1:c.2386G>T
NM_001130983.1:c.2293G>T
NM_001130984.1:c.2251G>T
NM_001130985.1:c.2344G>T
NM_001130986.1:c.2251G>T
NM_001130987.1:c.2344G>T
NM_003494.3:c.2290G>T
NM_001130455.2:c.2293G>T
NM_001130976.2:c.2248G>T
NM_001130977.2:c.2248G>T
NM_001130978.2:c.2290G>T
NM_001130979.2:c.2383G>T
NM_001130980.2:c.2341G>T
NM_001130981.2:c.2341G>T
NM_001130982.2:c.2386G>T
NM_001130983.2:c.2293G>T
NM_001130984.2:c.2251G>T
NM_001130985.2:c.2344G>T
NM_001130986.2:c.2251G>T
NM_003494.4:c.2290G>T
More

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PP4
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 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.2290G>T p.(Glu764Ter) variant in DYSF, which is also known as NM_001130987.2: c.2344G>T p.(Glu782Ter), is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 23/55, 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 an individual with suspected LGMD but above disease range dysferlin expression, where it was identified with a second presumed diagnostic variant in unknown phase (c.2638G>A p.(Glu880Lys), PMID: 30564623, LOVD Individual #00220801; Jain Foundation Dysferlin Registry internal data communication). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely 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 2.0.0; 01/23/2026): PVS1, PM2_Supporting.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PVS1
The NM_003494.4: c.2290G>T p.(Glu764Ter) variant in DYSF, which is also known as NM_001130987.2: c.2344G>T p.(Glu782Ter), is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 23/55, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). Splice AI=0.01
PP4
This variant has been identified in an individual with suspected LGMD, but with above disease range dysferlin expression, with a second presumed diagnostic variant in unknown phase (c.2638G>A p.(Glu880Lys), PMID: 30564623, LOVD Individual #00220801; Jain Foundation Dysferlin Registry internal data communication; PP4; PM3 not met). Given this individual had suspected LGMD with two presumably diagnostic variants, PP4 is applied at supporting strength.
Not Met criteria codes
PM3
This variant has been identified in an individual with suspected LGMD, but with above disease range dysferlin expression, with a second presumed diagnostic variant in unknown phase (c.2638G>A p.(Glu880Lys), PMID: 30564623, LOVD Individual #00220801; Jain Foundation Dysferlin Registry internal data communication; PP4; PM3 not met). c.2638G>A p.(Glu880Lys) is classified as VUS; given unknown phase, PM3 cannot be scored.
Curation History
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