Variant: NM_000232.5(SGCB):c.391C>T (p.Arg131Ter)

CA96782984

523842 (ClinVar)

Gene: SGCB

Condition: autosomal recessive limb-girdle muscular dystrophy

Inheritance Mode: Autosomal recessive inheritance

UUID: 7a042fc8-34d7-45cd-9672-801a7928929d

Approved on: 2025-01-08

Published on: 2025-01-08

HGVS expressions

NM_000232.5:c.391C>T
NM_000232.5(SGCB):c.391C>T (p.Arg131Ter)
NC_000004.12:g.52029716G>A
CM000666.2:g.52029716G>A
NC_000004.11:g.52895882G>A
CM000666.1:g.52895882G>A
NC_000004.10:g.52590639G>A
NG_008891.1:g.13604C>T
ENST00000381431.10:c.391C>T
ENST00000381431.9:c.391C>T
ENST00000506357.5:c.474C>T
ENST00000514133.1:c.468C>T
NM_000232.4:c.391C>T

Pathogenic

• Met criteria codes: PP4 PVS1 PM2_Supporting

• Not Met criteria codes: PS2 PS4 PS3 PS1 PP1 PP3 PP2 PM3 PM1 PM5 PM4 PM6 BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP4 BP1 BP3

Expert Panel

Limb Girdle Muscular Dystrophy VCEP

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

Evidence submitted by expert panel

Limb Girdle Muscular Dystrophy VCEP

The NM_000232.5: c.391C>T p.(Arg131Ter) variant in SGCB is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 3/6, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been identified in trans with second presumed diagnostic SGCB variant in one patient with progressive limb girdle muscle weakness and reduced expression of beta-sarcoglycan protein in skeletal muscle; however, the VCEP could not confirm the extent of the reduction (PP4; ClinVar SCV000748307.5 internal data communication). This variant is absent from gnomAD v2.1.1 and v.3.1.2 (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 1.0.0; 01/08/2025): PVS1, PP4, PM2_Supporting.

Met criteria codes

• PP4: This variant has been identified in trans with second presumed diagnostic SGCB variant in one patient with progressive limb girdle muscle weakness and reduced expression of alpha-sarcoglycan protein in skeletal muscle; however, the VCEP could not confirm the extent of the reduction (PP4; SCV000748307.5 internal communication).
• PVS1: The c.391C>T (p.Arg131Ter) variant in SGCB is a nonsense variant observed to cause a premature stop codon in biologically-relevant-exon 3/6 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
• PM2_Supporting: This variant is absent from gnomAD v2.1.1 and v.3.1.2 (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
• 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
• PS1: 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
• 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
• PM3: PM3 applied to c.265G>A p.(Val89Met) as pathogenic can be reached here without it.
• PM1: 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
• 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
• BA1: 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
• 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
• 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
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline