ClinVar Genomic variation as it relates to human health
NM_000231.3(SGCG):c.525del (p.Phe175fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000231.3(SGCG):c.525del (p.Phe175fs)
Variation ID: 189243 Accession: VCV000189243.58
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 13q12.12 13: 23295430 (GRCh38) [ NCBI UCSC ] 13: 23869569 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2015 Oct 20, 2024 Mar 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000231.3:c.525del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000222.2:p.Phe175fs frameshift NM_000231.2:c.525delT NM_001378244.1:c.579del NP_001365173.1:p.Phe193fs frameshift NM_001378245.1:c.525del NP_001365174.1:p.Phe175fs frameshift NM_001378246.1:c.525del NP_001365175.1:p.Phe175fs frameshift NC_000013.11:g.23295434del NC_000013.10:g.23869573del NG_008759.1:g.119514del LRG_207:g.119514del - Protein change
- F193fs
- Other names
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- Canonical SPDI
- NC_000013.11:23295429:TTTTT:TTTT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SGCG | - | - |
GRCh38 GRCh37 |
548 | 659 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (13) |
criteria provided, multiple submitters, no conflicts
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Mar 26, 2024 | RCV000169675.36 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 29, 2021 | RCV000713258.33 | |
SGCG-related congenital myopathy
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Likely pathogenic (1) |
criteria provided, single submitter
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Mar 1, 2024 | RCV004586589.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 15, 2014)
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criteria provided, single submitter
Method: clinical testing
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Limb girdle muscular dystrophy type 2C
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Study: CSER-MedSeq
Accession: SCV000221211.2 First in ClinVar: Apr 01, 2015 Last updated: Apr 01, 2015 |
Comment:
The Phe175LeufsX20 variant in SGCG has been reported in many individuals with limb girdle muscular dystrophy type 2C (LGMD2C; Noguchi 1995, Boyden 2010, Herson 2012, … (more)
The Phe175LeufsX20 variant in SGCG has been reported in many individuals with limb girdle muscular dystrophy type 2C (LGMD2C; Noguchi 1995, Boyden 2010, Herson 2012, Schroder 2014, El Kerch 2014). Data from large population studies is insufficient to assess the frequency of this variant. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 175 and leads to a premature termination codon 20 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Complete loss of SGCG function is an established disease mechanism in LGMD2C. In summary, this variant meets our criteria to be classified as pathogenic for LGMD2C in an autosomal recessive manner. (less)
Number of individuals with the variant: 1
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Pathogenic
(Dec 19, 2014)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV000843846.2
First in ClinVar: Oct 20, 2018 Last updated: Jan 26, 2021 |
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. The frequency … (more)
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity. Found in multiple individuals with expected phenotype for this gene. (less)
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Pathogenic
(Jul 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002789251.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001792557.3
First in ClinVar: Aug 21, 2021 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11693784, 18285821, 22367371, 17994539, 16832103, 23929688, 7481775, 16616845, 15954112, 14678800, 26404900, 25252238, 16916601, 22240777, 24552312, 12040521, 27759885, 30919934, 31130284, 31980526, 31127727, 8900232, 20623375, 19770540, 10942431, 32214227, 25214167, 32528171, 31589614) (less)
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Pathogenic
(Jun 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002021240.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806503.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Likely pathogenic
(Mar 01, 2024)
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criteria provided, single submitter
Method: research
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SGCG-related congenital myopathy
Affected status: yes
Allele origin:
biparental
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Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire
Accession: SCV005038501.1
First in ClinVar: Jul 15, 2024 Last updated: Jul 15, 2024 |
Comment:
PVS1+PM2
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Mar 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004201034.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001245659.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Aug 26, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000331677.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 11
Sex: mixed
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Pathogenic
(Dec 03, 2018)
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criteria provided, single submitter
Method: research
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Autosomal recessive limb-girdle muscular dystrophy type 2C
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001164546.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
Comment:
The homozygous p.Phe175LeufsTer20 variant in SGCG was identified by our study in five individuals (four siblings and one unrelated individual) with limb-girdle muscular dystrophy (LGMD). … (more)
The homozygous p.Phe175LeufsTer20 variant in SGCG was identified by our study in five individuals (four siblings and one unrelated individual) with limb-girdle muscular dystrophy (LGMD). This variant has been identified in 0.006092% (15/246240) of chromosomes in the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs765500509). Although this variant has been seen in the general population, the frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 175 and leads to a premature termination codon 20 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the SGCG gene is an established disease mechanism in autosomal recessive LGMD. This variant has also been reported in ClinVar (Variation ID: 189243). In summary, this variant meets criteria to be classified as pathogenic for LGMD in an autosomal recessive manner based on the predicted impact of the variant and multiple reports in ClinVar. ACMG/AMP Criteria applied: PM2, PVS1, PP1 (Richards 2015). (less)
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Pathogenic
(May 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002521573.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.006%). Frameshift: predicted to result in a loss … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.006%). Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000189243 / PMID: 7481775). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Proximal muscle weakness (present) , Urinary incontinence (present) , Inability to walk (present) , EMG: myopathic abnormalities (present)
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Pathogenic
(Nov 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002579640.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4_MOD, PM3, PM2_SUP, PP1
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Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000634388.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Phe175Leufs*20) in the SGCG gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Phe175Leufs*20) 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). This variant is present in population databases (rs765500509, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with limb girdle muscular dystrophy (PMID: 7481775, 12040521, 22240777, 23929688, 24552312). ClinVar contains an entry for this variant (Variation ID: 189243). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 12, 2000)
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no assertion criteria provided
Method: literature only
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MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 5
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022239.2
First in ClinVar: Apr 04, 2013 Last updated: Sep 28, 2018 |
Comment on evidence:
In 2 affected sibs from a Tunisian family with severe childhood autosomal recessive muscular dystrophy (LGMDR5; 253700) Ben Othmane et al. (1992), Noguchi et al. … (more)
In 2 affected sibs from a Tunisian family with severe childhood autosomal recessive muscular dystrophy (LGMDR5; 253700) Ben Othmane et al. (1992), Noguchi et al. (1995) identified a homozygous 1-bp deletion in the SGCG gene (which they designated 645delT). The same mutation was found in affected members of 2 additional Tunisian SCARMD families. The deletion changed the reading frame at codon 175, creating a premature stop signal at codon 193 and loss of a cluster of cysteine residues in the distal portion of the protein. Immunostaining of 1 patient's muscle showed a deficiency of alpha-, beta-, and gamma-sarcoglycan, indicating instability of the entire dystrophin-glycoprotein complex. McNally et al. (1996) identified an apparently homozygous 1-bp deletion in the gamma-sarcoglycan gene of a patient with LGMDR5. The deletion (which they designated 521delT) of a single T residue from a series of 5 T residues led to onset of symptoms at the age of 4 years. Crosbie et al. (2000) reported 2 sibs with limb-girdle muscular dystrophy and cardiomyopathy who were homozygous for a 1-bp deletion (525T) in the SGCG gene, causing a phe175-to-leu substitution followed by 18 missense amino acids and a premature stop codon at position 194. Assembly of the mutant gamma-sarcoglycan into a complex with alpha-, beta-, and delta-sarcoglycan and sarcospan was not affected. (less)
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Pathogenic
(Feb 22, 2017)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132481.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Pathogenic
(Aug 01, 2019)
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no assertion criteria provided
Method: research
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Autosomal recessive limb-girdle muscular dystrophy type 2C
Affected status: yes
Allele origin:
germline
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Section for Clinical Neurogenetics, University of Tübingen
Accession: SCV001156104.1
First in ClinVar: Apr 06, 2020 Last updated: Apr 06, 2020 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Limb-girdle muscular dystrophy type 2C
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001455353.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Exome sequencing in undiagnosed congenital myopathy reveals new genes and refines genes-phenotypes correlations. | de Feraudy Y | Genome medicine | 2024 | DOI: 10.1186/s13073-024-01353-0 |
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery. | Hengel H | European journal of human genetics : EJHG | 2020 | PMID: 32214227 |
Carrier frequency of the c.525delT mutation in the SGCG gene and estimated prevalence of limb girdle muscular dystrophy type 2C among the Moroccan population. | El Kerch F | Genetic testing and molecular biomarkers | 2014 | PMID: 24552312 |
Novel γ-sarcoglycan-mutation affects cardiac function and N-terminal dystrophin expression. | Schröder NW | Muscle & nerve | 2014 | PMID: 23929688 |
A phase I trial of adeno-associated virus serotype 1-γ-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C. | Herson S | Brain : a journal of neurology | 2012 | PMID: 22240777 |
Efficient identification of novel mutations in patients with limb girdle muscular dystrophy. | Boyden SE | Neurogenetics | 2010 | PMID: 20623375 |
Revised spectrum of mutations in sarcoglycanopathies. | Trabelsi M | European journal of human genetics : EJHG | 2008 | PMID: 18285821 |
Genotype-phenotype correlations in 35 Brazilian families with sarcoglycanopathies including the description of three novel mutations. | Moreira ES | Journal of medical genetics | 2003 | PMID: 12566530 |
[Muscular dystrophy due to a deficit of gamma-sarcoglycan. A report of three patients with the Delta-521t mutation]. | Eirís-Puñal J | Revista de neurologia | 2002 | PMID: 12040521 |
Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions. | Crosbie RH | Human molecular genetics | 2000 | PMID: 10942431 |
Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy. | McNally EM | Human molecular genetics | 1996 | PMID: 8923014 |
Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. | Noguchi S | Science (New York, N.Y.) | 1995 | PMID: 7481775 |
Linkage of Tunisian autosomal recessive Duchenne-like muscular dystrophy to the pericentromeric region of chromosome 13q. | Ben Othmane K | Nature genetics | 1992 | PMID: 1303286 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCG | - | - | - | - |
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Text-mined citations for rs786204786 ...
HelpRecord last updated Oct 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.