NM_000231.3(SGCG):c.87dup (p.Gly30fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2C

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jun 16, 2023
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:: RCV000002085.12

Allele description [Variation Report for NM_000231.3(SGCG):c.87dup (p.Gly30fs)]

NM_000231.3(SGCG):c.87dup (p.Gly30fs)

Gene:

SGCG:sarcoglycan gamma [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_000231.3(SGCG):c.87dup (p.Gly30fs)

HGVS:

NC_000013.11:g.23203781dup
NG_008759.1:g.27861dup
NM_000231.3:c.87dupMANE SELECT
NM_001378244.1:c.141dup
NM_001378245.1:c.87dup
NM_001378246.1:c.87dup
NP_000222.2:p.Gly30fs
NP_001365173.1:p.Gly48fs
NP_001365174.1:p.Gly30fs
NP_001365175.1:p.Gly30fs
LRG_207t1:c.87dup
LRG_207:g.27861dup
NC_000013.10:g.23777919_23777920insT
NC_000013.10:g.23777920dup
NM_000231.2:c.87dup
NM_000231.2:c.87dupT

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

G30fs

Links:

OMIM: 608896.0006; dbSNP: rs762777463

NCBI 1000 Genomes Browser:

rs762777463

Molecular consequence:

NM_000231.3:c.87dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378244.1:c.141dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378245.1:c.87dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378246.1:c.87dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMDR5)
Synonyms:: Limb-girdle muscular dystrophy with gamma-sarcoglycan deficiency; Muscular dystrophy, Duchenne-like; Duchenne-like muscular dystrophy, autosomal recessive, type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009677; MedGen: C0410173; Orphanet: 353; OMIM: 253700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022243	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2000)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8923014, 10874299
SCV001584145	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8923014, 27759885, 18285821, 28492532
SCV002021241	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004201067	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 24, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Private beta- and gamma-sarcoglycan gene mutations: evidence of a founder effect in Northern Italy.

Fanin M, Hoffman EP, Angelini C, Pegoraro E.

Hum Mutat. 2000;16(1):13-7.

PubMed [citation]

PMID:: 10874299

Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy.

McNally EM, Duggan D, Gorospe JR, Bönnemann CG, Fanin M, Pegoraro E, Lidov HG, Noguchi S, Ozawa E, Finkel RS, Cruse RP, Angelini C, Kunkel LM, Hoffman EP.

Hum Mol Genet. 1996 Nov;5(11):1841-7.

PubMed [citation]

PMID:: 8923014

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000022243.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

McNally et al. (1996) identified an apparently homozygous 1-bp insertion in the SGCG gene in a patient with limb-girdle muscular dystrophy (LGMDR5; 253700) who had onset of symptoms at age 7 years and was wheelchair-bound at age 14. The insertion (87insT) alters the reading frame of amino acid 30 and predicts addition of 29 missense amino acids and a stop codon, ablating the majority of the gamma-sarcoglycan protein.

Fanin et al. (2000) identified the same 1-bp insertion in the SGCG gene as the cause of limb-girdle muscular dystrophy in 6 unrelated families from northern Italy. Many patients were homozygotes, although they derived from nonconsanguineous marriages. The authors suggested that the mutant allele is a 'private' mutation in this geographic region. They identified another mutation, an 8-bp duplication in the beta-sarcoglycan gene (600900.0003), which likewise showed linkage disequilibrium with neighboring polymorphisms.

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

From Invitae, SCV001584145.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2008). This premature translational stop signal has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 8923014, 27759885). This variant is present in population databases (rs762777463, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gly30Trpfs*30) in the SGCG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCG are known to be pathogenic (PMID: 18285821).

#	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

From Revvity Omics, Revvity, SCV002021241.3

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

#	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

From Baylor Genetics, SCV004201067.1

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

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

Last Updated: Mar 16, 2024

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