NM_000231.3(SGCG):c.727_728del (p.Cys243fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2C

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 20, 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:: RCV000673041.9

Allele description [Variation Report for NM_000231.3(SGCG):c.727_728del (p.Cys243fs)]

NM_000231.3(SGCG):c.727_728del (p.Cys243fs)

Gene:

SGCG:sarcoglycan gamma [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_000231.3(SGCG):c.727_728del (p.Cys243fs)

HGVS:

NC_000013.11:g.23324388TG[2]
NG_008759.1:g.148468TG[2]
NM_000231.3:c.727_728delMANE SELECT
NM_001378244.1:c.781_782del
NM_001378245.1:c.727_728del
NM_001378246.1:c.727_728del
NP_000222.2:p.Cys243fs
NP_001365173.1:p.Cys261fs
NP_001365174.1:p.Cys243fs
NP_001365175.1:p.Cys243fs
LRG_207:g.148468TG[2]
NC_000013.10:g.23898527TG[2]
NC_000013.10:g.23898527_23898528del
NM_000231.2:c.727_728delTG

Protein change:

C243fs

Links:

dbSNP: rs758078849

Molecular consequence:

NM_000231.3:c.727_728del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378244.1:c.781_782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378245.1:c.727_728del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378246.1:c.727_728del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMDR5)
Synonyms:: MUSCULAR DYSTROPHY, DUCHENNE-LIKE; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 5
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
SCV000798207	Counsyl	no assertion criteria provided	Likely pathogenic (Mar 1, 2018)	unknown	clinical testing
SCV002247247	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 20, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 8923014, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000798207

Counsyl

no assertion criteria provided

Likely pathogenic
(Mar 1, 2018)

unknown

clinical testing

SCV002247247

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 20, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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

Details of each submission

From Counsyl, SCV000798207.2

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

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247247.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SGCG protein in which other variant(s) (p.Pro268Argfs*50) have been determined to be pathogenic (PMID: 8923014). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change results in a frameshift in the SGCG gene (p.Cys243Leufs*75). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the SGCG protein and extend the protein by 25 additional amino acid residues. This variant is present in population databases (rs758078849, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SGCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 556967).

#	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: Jul 5, 2025

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