NM_000231.3(SGCG):c.768del (p.Ser257fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2C

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 1, 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:: RCV000671426.5

Allele description [Variation Report for NM_000231.3(SGCG):c.768del (p.Ser257fs)]

NM_000231.3(SGCG):c.768del (p.Ser257fs)

Gene:

SGCG:sarcoglycan gamma [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_000231.3(SGCG):c.768del (p.Ser257fs)

HGVS:

NC_000013.11:g.23324433del
NG_008759.1:g.148513del
NM_000231.3:c.768delMANE SELECT
NM_001378244.1:c.822del
NM_001378245.1:c.768del
NM_001378246.1:c.768del
NP_000222.2:p.Ser257fs
NP_001365173.1:p.Ser275fs
NP_001365174.1:p.Ser257fs
NP_001365175.1:p.Ser257fs
LRG_207:g.148513del
NC_000013.10:g.23898572del
NM_000231.2:c.768delC

Protein change:

S257fs

Links:

dbSNP: rs1199421806

NCBI 1000 Genomes Browser:

rs1199421806

Molecular consequence:

NM_000231.3:c.768del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378244.1:c.822del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378245.1:c.768del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378246.1:c.768del - 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
SCV000796401	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Dec 20, 2017)	unknown	clinical testing	Citation Link,
SCV003461769	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 1, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10447257, 15322984, 22095924, 30107846, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000796401

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Dec 20, 2017)

unknown

clinical testing

Citation Link,

SCV003461769

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 1, 2023)

germline

clinical testing

PubMed (5)
[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

C283Y mutation and other C-terminal nucleotide changes in the gamma-sarcoglycan gene in the Bulgarian Gypsy population.

Todorova A, Ashikov A, Beltcheva O, Tournev I, Kremensky I.

Hum Mutat. 1999;14(1):40-4. Erratum in: Hum Mutat 2000;15(5):479.

PubMed [citation]

PMID:: 10447257

Mutation history of the roma/gypsies.

Morar B, Gresham D, Angelicheva D, Tournev I, Gooding R, Guergueltcheva V, Schmidt C, Abicht A, Lochmuller H, Tordai A, Kalmar L, Nagy M, Karcagi V, Jeanpierre M, Herczegfalvi A, Beeson D, Venkataraman V, Warwick Carter K, Reeve J, de Pablo R, Kucinskas V, Kalaydjieva L.

Am J Hum Genet. 2004 Oct;75(4):596-609. Epub 2004 Aug 20.

PubMed [citation]

PMID:: 15322984
PMCID:: PMC1182047

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000796401.1

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

#	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, SCV003461769.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

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.Cys283Tyr) have been determined to be pathogenic (PMID: 10447257, 15322984, 22095924). 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 creates a premature translational stop signal (p.Ser257Alafs*23) in the SGCG gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the SGCG protein. This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30107846). ClinVar contains an entry for this variant (Variation ID: 555584).

#	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: May 16, 2025

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