NM_000023.4(SGCA):c.229C>T (p.Arg77Cys) AND Sarcoglycanopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 18, 2018
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:: RCV000779225.13

Allele description [Variation Report for NM_000023.4(SGCA):c.229C>T (p.Arg77Cys)]

NM_000023.4(SGCA):c.229C>T (p.Arg77Cys)

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.229C>T (p.Arg77Cys)

HGVS:

NC_000017.11:g.50167653C>T
NG_008889.1:g.6649C>T
NM_000023.4:c.229C>TMANE SELECT
NM_001135697.3:c.229C>T
NP_000014.1:p.Arg77Cys
NP_000014.1:p.Arg77Cys
NP_001129169.1:p.Arg77Cys
LRG_203t1:c.229C>T
LRG_203:g.6649C>T
LRG_203p1:p.Arg77Cys
NC_000017.10:g.48245014C>T
NM_000023.2:c.229C>T
NM_000023.3:c.229C>T
NR_135553.2:n.265C>T
Q16586:p.Arg77Cys

Protein change:

R77C; ARG77CYS

Links:

UniProtKB: Q16586#VAR_010387; OMIM: 600119.0003; dbSNP: rs28933693

NCBI 1000 Genomes Browser:

rs28933693

Molecular consequence:

NM_000023.4:c.229C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001135697.3:c.229C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_135553.2:n.265C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Sarcoglycanopathy
Identifiers:: MONDO: MONDO:0016140; MedGen: C2936331

Recent activity

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insulin-induced gene 2 protein isoform a [Homo sapiens]
insulin-induced gene 2 protein isoform a [Homo sapiens]
gi|38327533|ref|NP_057217.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000915770	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Oct 18, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 27120200, 8528203, 9192266, 12746421, 15736300, 18252745, 18535179, 21856579 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000915770

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Pathogenic
(Oct 18, 2018)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D.

Fayssoil A, Ogna A, Chaffaut C, Chevret S, Guimarães-Costa R, Leturcq F, Wahbi K, Prigent H, Lofaso F, Nardi O, Clair B, Behin A, Stojkovic T, Laforet P, Orlikowski D, Annane D.

PLoS One. 2016;11(4):e0153095. doi: 10.1371/journal.pone.0153095.

PubMed [citation]

PMID:: 27120200
PMCID:: PMC4847860

A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal recessive limb-girdle muscular dystrophy.

Bueno MR, Moreira ES, Vainzof M, Chamberlain J, Marie SK, Pereira L, Akiyama J, Roberds SL, Campbell KP, Zatz M.

Hum Mol Genet. 1995 Jul;4(7):1163-7.

PubMed [citation]

PMID:: 8528203

See all PubMed Citations (8)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915770.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Across a selection of the available literature, the SGCA c.229C>T (p.Arg77Cys) variant has been identified in a homozygous state in at least 28 probands and in a compound heterozygous state in at least eight probands with limb-girdle muscular dystrophy (Bueno et al. 1995; Carrie et al. 1997; Boito et al. 2005; Hackman et al. 2005; Teatreault et al. 2011; Fayssoil et al. 2016). The p.Arg77Cys variant was reported in two of 624 controls and is reported at a frequency of 0.001949 in the European (Finnish) population from the Genome Aggregation Database. Functional studies in human cell lines showed that the p.Arg77Cys variant protein does not localize to the cell membrane, results in impaired assembly of the sarcoglycan complex, and is retained in the endoplasmic reticulum (Bartoli et al. 2008; Gastaldello et al. 2008). Based on the collective evidence, the p.Arg77Cys variant is classified as pathogenic for alpha-sarcoglycanopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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