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NM_000232.5(SGCB):c.271C>T (p.Arg91Cys) AND Autosomal recessive limb-girdle muscular dystrophy type 2E

Germline classification:
Pathogenic (5 submissions)
Last evaluated:
Feb 19, 2024
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:
RCV000813259.14

Allele description [Variation Report for NM_000232.5(SGCB):c.271C>T (p.Arg91Cys)]

NM_000232.5(SGCB):c.271C>T (p.Arg91Cys)

Gene:
SGCB:sarcoglycan beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q12
Genomic location:
Preferred name:
NM_000232.5(SGCB):c.271C>T (p.Arg91Cys)
HGVS:
  • NC_000004.12:g.52029836G>A
  • NG_008891.1:g.13484C>T
  • NM_000232.5:c.271C>TMANE SELECT
  • NP_000223.1:p.Arg91Cys
  • NP_000223.1:p.Arg91Cys
  • LRG_204t1:c.271C>T
  • LRG_204:g.13484C>T
  • LRG_204p1:p.Arg91Cys
  • NC_000004.11:g.52896002G>A
  • NM_000232.4:c.271C>T
Protein change:
R91C
Links:
dbSNP: rs555514820
NCBI 1000 Genomes Browser:
rs555514820
Molecular consequence:
  • NM_000232.5:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000953611Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 2, 2024)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001132480Counsyl
no assertion criteria provided
Likely pathogenic
(Apr 17, 2017)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001460964Natera, Inc.
no assertion criteria provided
Likely pathogenic
(Sep 16, 2020)
germlineclinical testing

SCV002019198Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Dec 16, 2022)
germlineclinical testing

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

SCV004208736Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Feb 19, 2024)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E).

Bönnemann CG, Passos-Bueno MR, McNally EM, Vainzof M, de Sá Moreira E, Marie SK, Pavanello RC, Noguchi S, Ozawa E, Zatz M, Kunkel LM.

Hum Mol Genet. 1996 Dec;5(12):1953-61.

PubMed [citation]
PMID:
8968749

LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3.

Bönnemann CG, Wong J, Ben Hamida C, Hamida MB, Hentati F, Kunkel LM.

Neuromuscul Disord. 1998 May;8(3-4):193-7.

PubMed [citation]
PMID:
9631401
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000953611.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 91 of the SGCB protein (p.Arg91Cys). This variant is present in population databases (rs555514820, gnomAD 0.01%). This missense change has been observed in individuals with limb-girdle muscular dystrophy (PMID: 9565988, 17994539). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 499193). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SGCB protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect SGCB function (PMID: 22095924). This variant disrupts the p.Arg91 amino acid residue in SGCB. Other variant(s) that disrupt this residue have been observed in individuals with SGCB-related conditions (PMID: 8968749, 9631401), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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

From Counsyl, SCV001132480.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV001460964.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Revvity Omics, Revvity, SCV002019198.3

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

From Baylor Genetics, SCV004208736.2

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

Last Updated: Jun 17, 2024