NM_000023.4(SGCA):c.292C>T (p.Arg98Cys) AND Autosomal recessive limb-girdle muscular dystrophy type 2D

Clinical significance:Pathogenic (Last evaluated: Dec 16, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000309945.4

Allele description [Variation Report for NM_000023.4(SGCA):c.292C>T (p.Arg98Cys)]

NM_000023.4(SGCA):c.292C>T (p.Arg98Cys)

Gene:
SGCA:sarcoglycan alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.33
Genomic location:
Preferred name:
NM_000023.4(SGCA):c.292C>T (p.Arg98Cys)
HGVS:
  • NC_000017.11:g.50167716C>T
  • NG_008889.1:g.6712C>T
  • NM_000023.4:c.292C>TMANE SELECT
  • NM_001135697.3:c.292C>T
  • NP_000014.1:p.Arg98Cys
  • NP_001129169.1:p.Arg98Cys
  • LRG_203t1:c.292C>T
  • LRG_203:g.6712C>T
  • NC_000017.10:g.48245077C>T
  • NM_000023.2:c.292C>T
  • NR_135553.2:n.328C>T
  • Q16586:p.Arg98Cys
Protein change:
R98C
Links:
UniProtKB: Q16586#VAR_010413; dbSNP: rs138945081
NCBI 1000 Genomes Browser:
rs138945081
Molecular consequence:
  • NM_000023.4:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001135697.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_135553.2:n.328C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy type 2D (LGMD2D)
Synonyms:
ADHALINOPATHY, PRIMARY; Limb-girdle muscular dystrophy, type 2D; Muscular dystrophy limb-girdle with alpha-sarcoglycan; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011968; MedGen: C2936332; Orphanet: 62; OMIM: 608099

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000797743Counsylno assertion criteria providedLikely pathogenic
(Feb 8, 2018)
unknownclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001217067Invitaecriteria provided, single submitter
Pathogenic
(Dec 16, 2019)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

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, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients.

Guglieri M, Magri F, D'Angelo MG, Prelle A, Morandi L, Rodolico C, Cagliani R, Mora M, Fortunato F, Bordoni A, Del Bo R, Ghezzi S, Pagliarani S, Lucchiari S, Salani S, Zecca C, Lamperti C, Ronchi D, Aguennouz M, Ciscato P, Di Blasi C, Ruggieri A, et al.

Hum Mutat. 2008 Feb;29(2):258-66.

PubMed [citation]
PMID:
17994539

Mutational spectrum of Chinese LGMD patients by targeted next-generation sequencing.

Yu M, Zheng Y, Jin S, Gang Q, Wang Q, Yu P, Lv H, Zhang W, Yuan Y, Wang Z.

PLoS One. 2017;12(4):e0175343. doi: 10.1371/journal.pone.0175343.

PubMed [citation]
PMID:
28403181
PMCID:
PMC5389788
See all PubMed Citations (12)

Details of each submission

From Counsyl, SCV000797743.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001217067.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

This sequence change replaces arginine with cysteine at codon 98 of the SGCA protein (p.Arg98Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs138945081, ExAC 0.03%). This variant has been observed in individual(s) with clinical features of SGCA-related conditions (PMID:7668821, 30107846, 9032047, 30764848). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 284708). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg98 amino acid residue in SGCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8069911, 7668821, 27120200, 22095924, 9192266, 12746421). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 10, 2021

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