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_000232.5(SGCB):c.699_702del (p.Phe233fs)

CA16040953

370474 (ClinVar)

Gene: SGCB
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
UUID: be814538-bc09-4bef-99d5-429d40398430
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_000232.5:c.699_702del
NM_000232.5(SGCB):c.699_702del (p.Phe233fs)
NC_000004.12:g.52028022_52028025del
CM000666.2:g.52028022_52028025del
NC_000004.11:g.52894188_52894191del
CM000666.1:g.52894188_52894191del
NC_000004.10:g.52588945_52588948del
NG_008891.1:g.15298_15301del
ENST00000381431.10:c.699_702del
ENST00000381431.9:c.699_702del
NM_000232.4:c.699_702del
More

Likely Pathogenic

Met criteria codes 5
PVS1_Strong PM2_Supporting PP4 PP1 PM3
Not Met criteria codes 21
BS2 BS3 BS1 BS4 BP4 BP1 BP3 BP2 BP5 BP7 PS1 PS2 PS4 PS3 BA1 PP3 PP2 PM5 PM1 PM4 PM6

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 SGCB 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_000232.5: c.699_702del p.(Phe233LeufsTer16) variant in SGCB is a frameshift variant that may cause loss of function of the protein; the resulting transcript is predicted to escape nonsense mediated decay but remove >10% of the protein (PVS1_Strong). This variant has been detected in at least two unrelated individuals with autosomal recessive limb girdle muscular dystrophy, including confirmed in trans with a likely pathogenic or pathogenic variant (c.377_384dup, 1 pt, PMID: 25862795) and in a homozygous state (0.25 pts, PMID: 25862795) (PM3). At least one patient with this variant and a second SGCB variant displayed progressive limb girdle muscle weakness as well as absent expression of beta-sarcoglycan protein, which is highly specific for SGCB-related LGMD; however, the presence of potentially diagnostic variants in all of the other sarcoglycan genes was not ruled out (PP4; PMID: 12868499, 25862795, 9032047). The variant has also been reported to segregate with autosomal recessive limb girdle muscular dystrophy in one affected family member (PP1; PMID: 25862795) and is absent from gnomAD v2.1.1 and v3.1.2 (PM2_Supporting). 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): PVS1_Strong, PM3, PP4, PP1, PM2_Supporting.
Met criteria codes
PVS1_Strong
The NM_000232.5: c.699_702del p.(Phe233LeufsTer16) variant in SGCB is a frameshift variant that may cause loss of function of the protein; the resulting transcript is predicted to escape nonsense mediated decay but remove >10% of the protein (PVS1_Strong).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v3.1.2 (PM2_Supporting).
PP4
At least one patient with this variant and a second SGCB variant displayed progressive limb girdle muscle weakness as well as absent expression of beta-sarcoglycan protein, which is highly specific for SGCB-related LGMD; however, the presence of potentially diagnostic variants in all of the other sarcoglycan genes was not ruled out (PP4; PMID: 12868499, 25862795, 9032047).
PP1
The variant has been reported to segregate with autosomal recessive limb girdle muscular dystrophy in one affected family member (PP1_Supporting; PMID: 25862795).
PM3
This variant has been detected in at least two unrelated individuals with autosomal recessive limb girdle muscular dystrophy, including confirmed in trans with a likely pathogenic or pathogenic variant (c.377_384dup, 1 pt, PMID: 25862795) and in a homozygous state (0.25 pts, PMID: 25862795) (PM3).
Not Met criteria codes
BS2
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
BS4
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
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
BP5
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
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
PS3
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
PP3
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
PM5
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
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
Curation History
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