ClinVar Miner

Submissions for variant NM_000232.5(SGCB):c.391C>T (p.Arg131Ter)

dbSNP: rs1013015106
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen RCV005000388 SCV005620298 pathogenic Autosomal recessive limb-girdle muscular dystrophy 2025-01-08 reviewed by expert panel curation 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.
GeneDx RCV000627315 SCV000748307 pathogenic not provided 2022-03-15 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31589614)
Labcorp Genetics (formerly Invitae), Labcorp RCV001209561 SCV001381001 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-06-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 523842). This variant has not been reported in the literature in individuals affected with SGCB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg131*) in the SGCB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCB are known to be pathogenic (PMID: 15938573, 18285821).
Revvity Omics, Revvity RCV001209561 SCV003808127 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-02-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV001209561 SCV004200988 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2024-02-09 criteria provided, single submitter clinical testing

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