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NM_000232.5(SGCB):c.552T>G (p.Tyr184Ter) AND Autosomal recessive limb-girdle muscular dystrophy type 2E

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Jul 7, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000009251.9

Allele description [Variation Report for NM_000232.5(SGCB):c.552T>G (p.Tyr184Ter)]

NM_000232.5(SGCB):c.552T>G (p.Tyr184Ter)

Gene:
SGCB:sarcoglycan beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q12
Genomic location:
Preferred name:
NM_000232.5(SGCB):c.552T>G (p.Tyr184Ter)
HGVS:
  • NC_000004.12:g.52028799A>C
  • NG_008891.1:g.14521T>G
  • NM_000232.5:c.552T>GMANE SELECT
  • NP_000223.1:p.Tyr184Ter
  • NP_000223.1:p.Tyr184Ter
  • LRG_204t1:c.552T>G
  • LRG_204:g.14521T>G
  • LRG_204p1:p.Tyr184Ter
  • NC_000004.11:g.52894965A>C
  • NM_000232.4:c.552T>G
Protein change:
Y184*; TYR184TER
Links:
OMIM: 600900.0002; dbSNP: rs104893868
NCBI 1000 Genomes Browser:
rs104893868
Molecular consequence:
  • NM_000232.5:c.552T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy type 2E (LGMDR4)
Synonyms:
Limb-girdle muscular dystrophy, type 2E; Muscular dystrophy limb-girdle with beta-sarcoglycan deficiency; Beta-sarcoglycan limb-girdle muscular dystrophy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011423; MedGen: C1858593; Orphanet: 119; OMIM: 604286

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029469OMIM
no assertion criteria provided
Pathogenic
(Nov 1, 1995)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000486102Counsyl
criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))
Likely pathogenic
(Mar 29, 2016)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV003525502Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 7, 2022)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.

Bönnemann CG, Modi R, Noguchi S, Mizuno Y, Yoshida M, Gussoni E, McNally EM, Duggan DJ, Angelini C, Hoffman EP.

Nat Genet. 1995 Nov;11(3):266-73. Erratum in: Nat Genet 1996 Jan;12(1):110.

PubMed [citation]
PMID:
7581449

Mutations in the sarcoglycan genes in patients with myopathy.

Duggan DJ, Gorospe JR, Fanin M, Hoffman EP, Angelini C.

N Engl J Med. 1997 Feb 27;336(9):618-24.

PubMed [citation]
PMID:
9032047
See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000029469.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a child with an autosomal recessive muscular dystrophy (LGMDR4; 604286), the only child of clinically unaffected and unrelated parents of Italian background, Bonnemann et al. (1995) found compound heterozygosity for 2 mutations in the SGCB gene: a T-to-G transversion, resulting in a tyr184-to-ter (Y184X) nonsense mutation, inherited from the mother, and an 8-bp duplication after codon 125 (600900.0003), resulting in frameshift and a premature termination at codon 129, inherited from the father. Both mutations were predicted to severely truncate the protein, ablating most of its extracellular domain. At age 1 year, the patient had an increased serum creatine phosphokinase (CPK) without symptoms. Persistent elevation of CPK values prompted muscle biopsy at 13 months of age, which showed fiber size variation, scattered degenerating and regenerating muscle fibers, and mild increase in perimysial tissue. Reassessment at 40 months of age revealed signs of muscle weakness: she used a modified Gowers maneuver to get up from the floor and rolled onto her side to go from a lying into a sitting position. She had mild scapular winging and firmness of her calf muscles.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000486102.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV003525502.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 8713). This premature translational stop signal has been observed in individual(s) with SGCB-related conditions (PMID: 7581449, 9032047, 12868499, 25862795). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr184*) 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 14, 2024