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.1867C>T (p.Gln623Ter)

CA253901

6665 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: 976d5508-20a4-411e-b250-1c0288ee17ab
Approved on: 2025-12-29
Published on: 2026-01-12

HGVS expressions

NM_001130987.2(DYSF):c.1867C>T (p.Gln623Ter)
NM_001130987.2:c.1867C>T
NC_000002.12:g.71553071C>T
CM000664.2:g.71553071C>T
NC_000002.11:g.71780201C>T
CM000664.1:g.71780201C>T
NC_000002.10:g.71633709C>T
NG_008694.1:g.104449C>T
ENST00000258104.8:c.1813C>T
ENST00000410020.8:c.1867C>T
ENST00000258104.7:c.1813C>T
ENST00000394120.6:c.1816C>T
ENST00000409366.5:c.1816C>T
ENST00000409582.7:c.1864C>T
ENST00000409651.5:c.1909C>T
ENST00000409744.5:c.1774C>T
ENST00000409762.5:c.1864C>T
ENST00000410020.7:c.1867C>T
ENST00000410041.1:c.1867C>T
ENST00000413539.6:c.1906C>T
ENST00000429174.6:c.1813C>T
NM_001130455.1:c.1816C>T
NM_001130976.1:c.1771C>T
NM_001130977.1:c.1771C>T
NM_001130978.1:c.1813C>T
NM_001130979.1:c.1906C>T
NM_001130980.1:c.1864C>T
NM_001130981.1:c.1864C>T
NM_001130982.1:c.1909C>T
NM_001130983.1:c.1816C>T
NM_001130984.1:c.1774C>T
NM_001130985.1:c.1867C>T
NM_001130986.1:c.1774C>T
NM_001130987.1:c.1867C>T
NM_003494.3:c.1813C>T
NM_001130455.2:c.1816C>T
NM_001130976.2:c.1771C>T
NM_001130977.2:c.1771C>T
NM_001130978.2:c.1813C>T
NM_001130979.2:c.1906C>T
NM_001130980.2:c.1864C>T
NM_001130981.2:c.1864C>T
NM_001130982.2:c.1909C>T
NM_001130983.2:c.1816C>T
NM_001130984.2:c.1774C>T
NM_001130985.2:c.1867C>T
NM_001130986.2:c.1774C>T
NM_003494.4:c.1813C>T
More

Pathogenic

Met criteria codes 4
PM3_Supporting PP4_Strong PVS1 PM2_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.1813C>T p.(Gln605Ter) variant in DYSF, which is also known as NM_001130987.2: c.1867C>T (p.Gln623Ter), is a stop-gained variant expected to introduce a premature stop codon in exon 20/55, leading to nonsense mediated decay in a gene in which loss of function is a known disease mechanism (PVS1). This variant has been reported in at least three patients with features consistent with LGMD or dysferlinopathy (PMID: 9731526, 17129727, 17828519, 33715265), including in a homozygous state without reported familial consanguinity (0.5 pts, PMID: 9731526) (PM3_Supporting). At least one patient with this variant and a second presumed diagnostic DYSF variant exhibited both progressive limb girdle muscle weakness and absent or significantly reduced dysferlin protein expression in skeletal muscle or blood monocytes, which is highly specific for DYSF-related LGMD (PMID: 33715265; PP4_Strong). This variant is 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 (LGMD VCEP specifications version 2.0.0; 12/29/2025): PVS1, PM3_Supporting, PP4_Strong, PM2_Supporting.
Met criteria codes
PM3_Supporting
This variant has been reported in at least three patients with features consistent with LGMD or dysferlinopathy (PMID: 9731526, 17129727, 17828519, 33715265), including in a homozygous state without reported familial consanguinity (0.5 pts, PMID: 9731526) (PM3_Supporting).
PP4_Strong
At least one patient with this variant and a second presumed diagnostic DYSF variant exhibited both progressive limb girdle muscle weakness and absent or significantly reduced dysferlin protein expression in skeletal muscle or blood monocytes, which is highly specific for DYSF-related LGMD (PMID: 33715265; PP4_Strong).
PVS1
The NM_003494.4: c.1813C>T p.(Gln605Ter) variant in DYSF, which is also known as NM_001130987.2: c.1867C>T (p.Gln623Ter), is a stop-gained variant expected to introduce a premature stop codon in exon 20/55, leading to nonsense mediated decay in a gene in which loss of function is a known disease mechanism (PVS1). SpliceAI 0.01
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_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.