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NM_000023.4(SGCA):c.269A>G (p.Tyr90Cys) AND Autosomal recessive limb-girdle muscular dystrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 16, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003123566.3

Allele description [Variation Report for NM_000023.4(SGCA):c.269A>G (p.Tyr90Cys)]

NM_000023.4(SGCA):c.269A>G (p.Tyr90Cys)

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.269A>G (p.Tyr90Cys)
HGVS:
  • NC_000017.11:g.50167693A>G
  • NG_008889.1:g.6689A>G
  • NM_000023.4:c.269A>GMANE SELECT
  • NM_001135697.3:c.269A>G
  • NP_000014.1:p.Tyr90Cys
  • NP_000014.1:p.Tyr90Cys
  • NP_001129169.1:p.Tyr90Cys
  • LRG_203t1:c.269A>G
  • LRG_203:g.6689A>G
  • LRG_203p1:p.Tyr90Cys
  • NC_000017.10:g.48245054A>G
  • NM_000023.2:c.269A>G
  • NM_000023.2:c.269A>G
  • NM_000023.3:c.269A>G
  • NR_135553.2:n.305A>G
Protein change:
Y90C
Molecular consequence:
  • NM_000023.4:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001135697.3:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_135553.2:n.305A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy
Identifiers:
MONDO: MONDO:0015152; MedGen: C2931907; OMIM: PS253600

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003801330Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Jan 16, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications.

Soheili T, Gicquel E, Poupiot J, N'Guyen L, Le Roy F, Bartoli M, Richard I.

Hum Mutat. 2012 Feb;33(2):429-39. doi: 10.1002/humu.21659. Epub 2011 Dec 22.

PubMed [citation]
PMID:
22095924

Sarcolemmal alpha and gamma sarcoglycan protein deficiencies in Turkish siblings with a novel missense mutation in the alpha sarcoglycan gene.

Diniz G, Tosun Yildirim H, Akinci G, Hazan F, Ozturk A, Yararbas K, Tukun A.

Pediatr Neurol. 2014 Jun;50(6):640-7. doi: 10.1016/j.pediatrneurol.2013.12.024. Epub 2014 Jan 25.

PubMed [citation]
PMID:
24742800
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003801330.2

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

Description

Variant summary: SGCA c.269A>G (p.Tyr90Cys) results in a non-conservative amino acid change located in the Dystroglycan-type cadherin-like domain (IPR006644) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249164 control chromosomes (gnomAD). c.269A>G has been reported in the literature in two homozygous individuals from the same family, who were affected with Limb-Girdle Muscular Dystrophy (Moreira_2003). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, and demonstrated the complete lack of the protein at the cell surface, while the variant protein was visible intracellularly when immunostaining is performed on permeabilized cells (Soheili_2012). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Sep 29, 2024