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]
  • No ClinVar Id was directly found from the curated document
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_003494.4:c.5093C>T

CA347220971

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: a4aef42d-297b-4854-8fc3-a704114a43a4
Approved on: 2026-01-23
Published on: 2026-02-17

HGVS expressions

NM_003494.4:c.5093C>T
NC_000002.12:g.71665197C>T
CM000664.2:g.71665197C>T
NC_000002.11:g.71892327C>T
CM000664.1:g.71892327C>T
NC_000002.10:g.71745835C>T
NG_008694.1:g.216575C>T
ENST00000698057.1:c.2624C>T
ENST00000698058.1:c.1841C>T
ENST00000698059.1:c.1949C>T
ENST00000258104.8:c.5093C>T
ENST00000410020.8:c.5210C>T
ENST00000258104.7:c.5093C>T
ENST00000394120.6:c.5096C>T
ENST00000409366.5:c.5159C>T
ENST00000409582.7:c.5207C>T
ENST00000409651.5:c.5189C>T
ENST00000409744.5:c.5117C>T
ENST00000409762.5:c.5144C>T
ENST00000410020.7:c.5210C>T
ENST00000410041.1:c.5147C>T
ENST00000413539.6:c.5186C>T
ENST00000429174.6:c.5156C>T
ENST00000479049.6:n.1978C>T
NM_001130455.1:c.5096C>T
NM_001130976.1:c.5051C>T
NM_001130977.1:c.5114C>T
NM_001130978.1:c.5156C>T
NM_001130979.1:c.5186C>T
NM_001130980.1:c.5144C>T
NM_001130981.1:c.5207C>T
NM_001130982.1:c.5189C>T
NM_001130983.1:c.5159C>T
NM_001130984.1:c.5117C>T
NM_001130985.1:c.5147C>T
NM_001130986.1:c.5054C>T
NM_001130987.1:c.5210C>T
NM_003494.3:c.5093C>T
NM_001130987.2:c.5210C>T
NM_001130455.2:c.5096C>T
NM_001130976.2:c.5051C>T
NM_001130977.2:c.5114C>T
NM_001130978.2:c.5156C>T
NM_001130979.2:c.5186C>T
NM_001130980.2:c.5144C>T
NM_001130981.2:c.5207C>T
NM_001130982.2:c.5189C>T
NM_001130983.2:c.5159C>T
NM_001130984.2:c.5117C>T
NM_001130985.2:c.5147C>T
NM_001130986.2:c.5054C>T
More

Likely Pathogenic

Met criteria codes 4
PM2_Supporting PP3 PP4_Strong PM3_Supporting
Not Met criteria codes 2
PM5 PS3

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.5093C>T variant in DYSF, which is also known as NM_001130987.2: c.5210C>T p.(Pro1737Leu), is a missense variant predicted to cause substitution of proline to leucine at amino acid 1698, p.(Pro1698Leu). This variant has been observed in one individual with suspected LGMD with a second pathogenic variant in unknown phase (NM_003494.4: c.2875C>T p.(Arg959Trp), 0.5 pts, PMID: 33927379; PM3_Supporting). This individual also had absent dysferlin expression in muscle, which is highly specific for DYSF-related LGMD (PP4_Strong). This variant is absent in gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.87, which is above the LGMD VCEP threshold of ≥0.70, evidence that correlates with impact to DYSF function (PP3). In summary, this variant is 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 (specifications v2.0.0; 01/23/2026): PM3_Supporting, PP4_Strong, PP3, PM2_Supporting.
Met criteria codes
PM2_Supporting
This variant is absent in gnomAD v4.1.0 (PM2_Supporting).
PP3
The computational predictor REVEL gives a score of 0.87, which is above the LGMD VCEP threshold of ≥0.70, evidence that correlates with impact to DYSF function (PP3). Splice AI=0.00
PP4_Strong
This individual also had absent dysferlin expression in muscle, which is highly specific for DYSF-related LGMD (PP4_strong).
PM3_Supporting
This variant has been observed in one individual with suspected LGMD with a second pathogenic variant in unknown phase (c.2875C>T p.(Arg959Trp), 0.5 pts, PMID: 33927379; PM3_Supporting). c.2875C>T p.(Arg959Trp) is independently pathogenic without this case.
Not Met criteria codes
PM5
Another variant at this position, c.5093C>G p.(Pro1698Arg), is classified as LP, but with the use of PM5 based on the current variant. In addition, there is another variant p.(Pro1698Ser) that looks like it will not go above VUS (not curated). Therefore PM5 is not applicable.
PS3
Not in the Tominaga study. No additional functional studies.
Curation History
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