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.4282C>T (p.Gln1428Ter)

CA1706954

285153 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: aab3c348-66cf-4f14-b09e-6878ec67455d
Approved on: 2025-09-30
Published on: 2025-10-09

HGVS expressions

NM_001130987.2:c.4282C>T
NM_001130987.2(DYSF):c.4282C>T (p.Gln1428Ter)
NC_000002.12:g.71612701C>T
CM000664.2:g.71612701C>T
NC_000002.11:g.71839831C>T
CM000664.1:g.71839831C>T
NC_000002.10:g.71693339C>T
NG_008694.1:g.164079C>T
ENST00000698057.1:c.1696C>T
ENST00000698058.1:c.913C>T
ENST00000698059.1:c.871C>T
ENST00000258104.8:c.4228C>T
ENST00000410020.8:c.4282C>T
ENST00000258104.7:c.4228C>T
ENST00000394120.6:c.4231C>T
ENST00000409366.5:c.4231C>T
ENST00000409582.7:c.4279C>T
ENST00000409651.5:c.4324C>T
ENST00000409744.5:c.4189C>T
ENST00000409762.5:c.4279C>T
ENST00000410020.7:c.4282C>T
ENST00000410041.1:c.4282C>T
ENST00000413539.6:c.4321C>T
ENST00000429174.6:c.4228C>T
ENST00000468173.1:n.464C>T
ENST00000479049.6:n.1113C>T
ENST00000487180.5:n.447C>T
ENST00000494501.5:n.526C>T
NM_001130455.1:c.4231C>T
NM_001130976.1:c.4186C>T
NM_001130977.1:c.4186C>T
NM_001130978.1:c.4228C>T
NM_001130979.1:c.4321C>T
NM_001130980.1:c.4279C>T
NM_001130981.1:c.4279C>T
NM_001130982.1:c.4324C>T
NM_001130983.1:c.4231C>T
NM_001130984.1:c.4189C>T
NM_001130985.1:c.4282C>T
NM_001130986.1:c.4189C>T
NM_001130987.1:c.4282C>T
NM_003494.3:c.4228C>T
NM_001130455.2:c.4231C>T
NM_001130976.2:c.4186C>T
NM_001130977.2:c.4186C>T
NM_001130978.2:c.4228C>T
NM_001130979.2:c.4321C>T
NM_001130980.2:c.4279C>T
NM_001130981.2:c.4279C>T
NM_001130982.2:c.4324C>T
NM_001130983.2:c.4231C>T
NM_001130984.2:c.4189C>T
NM_001130985.2:c.4282C>T
NM_001130986.2:c.4189C>T
NM_003494.4:c.4228C>T
More

Pathogenic

Met criteria codes 4
PM3_Supporting PVS1 PP4 PP1
Not Met criteria codes 1
PM2

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.4228C>T p.(Gln1410Ter) variant in DYSF, which is also known as NM_001130987.2: c.4282C>T (p.Gln1428Ter), is a nonsense variant predicted to introduce a premature stop codon in exon 39/55, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been observed in four individuals with features of LGMD from two families (PMID: 35047756, 34624274). In a consanguineous family from Jordan, it was identified in a homozygous state in two affected siblings (PMID: 35047756; PP1). In the affected child of one of the homozygous individuals, it was also identified in unconfirmed phase with a pathogenic variant (NM_003494.4: c.4022T>C p.(Leu1341Pro), 0.5 pts; PM3_Supporting). At least one patient with this variant and a second presumed diagnostic DYSF allele displayed progressive proximal muscle weakness or had a clinical diagnosis of LGMD (PMID: 35047756, 34624274; PP4). The filtering allele frequency for this variant is 0.0001752 in gnomAD v4.1.0 (the upper bound of the 95% confidence interval of 5/60012 Admixed American alleles), which is higher than the VCEP threshold of 0.0001 for PM2_Supporting (criterion not met). 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; 09/30/2025): PVS1, PP1, PM3_Supporting, PP4.
Met criteria codes
PM3_Supporting
This variant has been observed in four individuals with features of LGMD from two families (PMID: 35047756, 34624274). In a consanguineous family from Jordan, it was identified in a homozygous state in two affected siblings (PMID: 35047756; PP1). In the affected child of one of the homozygous individuals, it was also identified in unconfirmed phase with a pathogenic variant (NM_003494.4: c.4022T>C p.(Leu1341Pro), 0.5 pts; PM3_Supporting).
PVS1
The NM_003494.4: c.4228C>T p.(Gln1410Ter) variant in DYSF, which is also known as NM_001130987.2: c.4282C>T (p.Gln1428Ter), is a nonsense variant predicted to introduce a premature stop codon in exon 39/55, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1).
PP4
At least one patient with this variant and a second presumed diagnostic DYSF allele displayed progressive proximal muscle weakness or had a clinical diagnosis of LGMD (PMID: 35047756, 34624274; PP4).
PP1
This variant was shown to co-segregate with autosomal recessive LGMD in one affected family member (PMID: 34624274, PP1).
Not Met criteria codes
PM2
The filtering allele frequency for this variant is 0.0001752 in gnomAD v4.1.0 (the upper bound of the 95% confidence interval of 5/60012 Admixed American alleles), which is higher than the VCEP threshold of 0.0001 for PM2_Supporting (criterion not met).
Curation History
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