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.2426C>T (p.Pro809Leu)

CA49742304

566085 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: limb-girdle muscular dystrophy (MONDO:0016971)
Inheritance Mode: Autosomal recessive inheritance
UUID: f3a996a4-fbe5-4ea1-afbf-d481d523ba99
Approved on: 2026-04-30
Published on: 2026-05-07

HGVS expressions

NM_001130987.2(DYSF):c.2426C>T (p.Pro809Leu)
NM_001130987.2:c.2426C>T
NC_000002.12:g.71564074C>T
CM000664.2:g.71564074C>T
NC_000002.11:g.71791204C>T
CM000664.1:g.71791204C>T
NC_000002.10:g.71644712C>T
NG_008694.1:g.115452C>T
ENST00000258104.8:c.2372C>T
ENST00000410020.8:c.2426C>T
ENST00000258104.7:c.2372C>T
ENST00000394120.6:c.2375C>T
ENST00000409366.5:c.2375C>T
ENST00000409582.7:c.2423C>T
ENST00000409651.5:c.2468C>T
ENST00000409744.5:c.2333C>T
ENST00000409762.5:c.2423C>T
ENST00000410020.7:c.2426C>T
ENST00000410041.1:c.2426C>T
ENST00000413539.6:c.2465C>T
ENST00000429174.6:c.2372C>T
NM_001130455.1:c.2375C>T
NM_001130976.1:c.2330C>T
NM_001130977.1:c.2330C>T
NM_001130978.1:c.2372C>T
NM_001130979.1:c.2465C>T
NM_001130980.1:c.2423C>T
NM_001130981.1:c.2423C>T
NM_001130982.1:c.2468C>T
NM_001130983.1:c.2375C>T
NM_001130984.1:c.2333C>T
NM_001130985.1:c.2426C>T
NM_001130986.1:c.2333C>T
NM_001130987.1:c.2426C>T
NM_003494.3:c.2372C>T
NM_001130455.2:c.2375C>T
NM_001130976.2:c.2330C>T
NM_001130977.2:c.2330C>T
NM_001130978.2:c.2372C>T
NM_001130979.2:c.2465C>T
NM_001130980.2:c.2423C>T
NM_001130981.2:c.2423C>T
NM_001130982.2:c.2468C>T
NM_001130983.2:c.2375C>T
NM_001130984.2:c.2333C>T
NM_001130985.2:c.2426C>T
NM_001130986.2:c.2333C>T
NM_003494.4:c.2372C>T
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Uncertain Significance

Met criteria codes 3
PM5_Supporting PM2_Supporting PP3
Not Met criteria codes 3
PM3 PS3 PP4

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.2372C>T variant in DYSF, which is also known as NM_001130987.2: c.2426C>T p.(Pro809Leu) is a missense variant expected to cause the substitution of proline for leucine at amino acid 791, p.(Pro791Leu). To our knowledge, this variant has not been reported in association with limb girdle muscular dystrophy. The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.0 is 0.000014 (10/1180030 European (non-Finnish) chromosomes), which is less than the LGMD VCEP threshold (0.0001), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.86, which exceeds the threshold of ≥0.70, evidence that correlates with impact to DYSF function. In addition, another missense variant at this position, NM_003494.4: c.2372C>G p.(Pro791Arg), has been classified as likely pathogenic for limb girdle muscular dystrophy by the LGMD VCEP (PM5_Supporting). In summary, at this time there is insufficient evidence to classify this variant as pathogenic or benign, and it remains a variant of uncertain significance 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; 04/30/2026): PM2_Supporting, PP3, PM5_Supporting.
Met criteria codes
PM5_Supporting
Another missense variant at this position, NM_003494.4: c.2372C>G p.(Pro791Arg), has been classified as likely pathogenic for limb girdle muscular dystrophy by the LGMD VCEP (PM5_Supporting). PP3 applies to both variants neither variant is predicted to affect splicing do not affect first or last amino acid of an exon c.2372C>A p.(Pro791Gln) not in LOVD, not in Dysferlin Registry, LP by Labcorp Genetics (formerly Invitae), Labcorp in ClinVar but no literature citations (looks to be based on PM5 for c.2372C>G p.(Pro791Arg)
PM2_Supporting
The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.0 is 0.000014 (10/1180030 European (non-Finnish) chromosomes), which is less than the LGMD VCEP threshold (0.0001), meeting this criterion (PM2_Supporting).
PP3
The computational predictor REVEL gives a score of 0.86, which exceeds the threshold of ≥0.70, evidence that correlates with impact to DYSF function.
Not Met criteria codes
PM3
To our knowledge, this variant has not been reported in association with limb girdle muscular dystrophy. not in LOVD no literature identified not in Dysferlin Registry
PS3
not evaluated in Tominaga et al.
PP4
To our knowledge, this variant has not been reported in association with limb girdle muscular dystrophy.
Curation History
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