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_000231.3(SGCG):c.158T>C (p.Leu53Pro)

CA10606508

289650 (ClinVar)

Gene: SGCG
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a9986917-d116-4447-ad38-457f1d07503a
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_000231.3:c.158T>C
NM_000231.3(SGCG):c.158T>C (p.Leu53Pro)
NC_000013.11:g.23203852T>C
CM000675.2:g.23203852T>C
NC_000013.10:g.23777991T>C
CM000675.1:g.23777991T>C
NC_000013.9:g.22675991T>C
NG_008759.1:g.27932T>C
ENST00000218867.4:c.158T>C
ENST00000218867.3:c.158T>C
NM_000231.2:c.158T>C
NM_001378244.1:c.212T>C
NM_001378245.1:c.158T>C
NM_001378246.1:c.158T>C
More

Likely Pathogenic

Met criteria codes 4
PP3 PM3 PP4_Strong PM2_Supporting
Not Met criteria codes 22
PS2 PS3 PS1 PS4 PP1 PP2 PM1 PM5 PM4 PM6 PVS1 BS2 BS4 BS3 BS1 BP3 BP2 BP4 BP1 BP7 BP5 BA1

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 SGCG Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Limb Girdle Muscular Dystrophy VCEP
The NM_000231.3: c.158T>C variant in SGCG is a missense variant predicted to cause substitution of leucine by proline at amino acid 53 (p.Leu53Pro). This variant has been detected in at least three individuals with autosomal recessive limb girdle muscular dystrophy (PMID: 30564623, 18996010), including in a homozygous state in two patients (1.0 pt, PMID: 18996010) (PM3). At least one patient with this variant displayed progressive limb girdle muscle weakness and reduced expression of gamma sarcoglycan protein in skeletal muscle, which is highly specific for SGCG-related LGMD (PP4_Strong; PMID: 18996010). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008 (1/113696 alleles) in the European (non-Finnish) population, which is lower than the ClinGen LGMD VCEP threshold (≤0.00009) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.98, which exceeds the threshold of ≥0.70, evidence that correlates with impact to SGCG function (PP3). 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 1.0.0; 01/08/2025): PP4_Strong, PM3, PM2_supporting, PP3.
Met criteria codes
PP3
The computational predictor REVEL gives a score of 0.978, which meets the threshold of ≥0.70, evidence that correlates with impact to SGCG function (PP3).
PM3
This variant has been detected in 3 individuals with autosomal recessive limb-girdle muscular dystrophy. 2 individuals were homozygous for the variant (1.0pt, PMID: 18996010) (PM3).
PP4_Strong
At least one patient with this variant displayed progressive limb girdle muscle weakness and reduced expression of gamma sarcoglycan protein in skeletal muscle, which is highly specific for SGCG-related LGMD (PP4_Strong; PMID: 18996010).
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008 (1/113696 alleles) in the European (non-Finnish) population, which is lower than the ClinGen LGMD VCEP threshold (≤0.00009) for PM2_Supporting, meeting this criterion (PM2_Supporting).
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Another missense variant c.157C>T (p.Leu53Phe) in the same codon has been reported (ClinVar Variation ID 461622). However, this variant has not yet met the criteria to be classified as pathogenic or likely pathogenic by the ClinGen LGMD VCEP (PM5 not met).
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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