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NM_000232.5(SGCB):c.551A>G (p.Tyr184Cys) AND Autosomal recessive limb-girdle muscular dystrophy type 2E

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Jan 22, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV000642670.8

Allele description [Variation Report for NM_000232.5(SGCB):c.551A>G (p.Tyr184Cys)]

NM_000232.5(SGCB):c.551A>G (p.Tyr184Cys)

Gene:
SGCB:sarcoglycan beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q12
Genomic location:
Preferred name:
NM_000232.5(SGCB):c.551A>G (p.Tyr184Cys)
HGVS:
  • NC_000004.12:g.52028800T>C
  • NG_008891.1:g.14520A>G
  • NM_000232.5:c.551A>GMANE SELECT
  • NP_000223.1:p.Tyr184Cys
  • NP_000223.1:p.Tyr184Cys
  • LRG_204t1:c.551A>G
  • LRG_204:g.14520A>G
  • LRG_204p1:p.Tyr184Cys
  • NC_000004.11:g.52894966T>C
  • NM_000232.4:c.551A>G
Protein change:
Y184C
Links:
dbSNP: rs1365923535
NCBI 1000 Genomes Browser:
rs1365923535
Molecular consequence:
  • NM_000232.5:c.551A>G - 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
SCV000764357Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 22, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000789305Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))
Uncertain significance
(Jan 26, 2017)
unknownclinical testing

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

Citation Link

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

Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients.

Xie Z, Hou Y, Yu M, Liu Y, Fan Y, Zhang W, Wang Z, Xiong H, Yuan Y.

Orphanet J Rare Dis. 2019 Feb 14;14(1):43. doi: 10.1186/s13023-019-1021-9.

PubMed [citation]
PMID:
30764848
PMCID:
PMC6376703

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000764357.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 184 of the SGCB protein (p.Tyr184Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 10660328, 30764848; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 534948). 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%. 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, SCV000789305.1

#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: Jul 15, 2024