ClinVar Genomic variation as it relates to human health
NM_000232.5(SGCB):c.31C>G (p.Gln11Glu)
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_000232.5(SGCB):c.31C>G (p.Gln11Glu)
Variation ID: 282248 Accession: VCV000282248.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q12 4: 52038229 (GRCh38) [ NCBI UCSC ] 4: 52904395 (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 Dec 6, 2016 Feb 4, 2024 Oct 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000232.5:c.31C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000223.1:p.Gln11Glu missense NC_000004.12:g.52038229G>C NC_000004.11:g.52904395G>C NG_008891.1:g.5091C>G LRG_204:g.5091C>G LRG_204t1:c.31C>G LRG_204p1:p.Gln11Glu Q16585:p.Gln11Glu - Protein change
- Q11E
- Other names
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- Canonical SPDI
- NC_000004.12:52038228:G:C
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD), exomes 0.00023
Exome Aggregation Consortium (ExAC) 0.00074
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
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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LOC129992585 | - | - | - | GRCh38 | - | 97 |
SGCB | - | - |
GRCh38 GRCh37 |
492 | 602 |
Conditions - Germline
Condition
Help
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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Uncertain significance (1) |
criteria provided, single submitter
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Jul 19, 2016 | RCV000261367.5 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 8, 2021 | RCV000399677.6 | |
Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
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Oct 10, 2023 | RCV000543057.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 24, 2022 | RCV002229741.1 |
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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Uncertain significance
(Jun 06, 2017)
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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: SCV000333606.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 7
Sex: mixed
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Uncertain significance
(Jul 19, 2016)
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criteria provided, single submitter
Method: clinical testing
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Beta-sarcoglycanopathy
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000449675.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The SGCB c.31C>G (p.Gln11Glu) variant has been reported in one study and was found in a homozygous state in a 14-year-old male with Duchenne muscular … (more)
The SGCB c.31C>G (p.Gln11Glu) variant has been reported in one study and was found in a homozygous state in a 14-year-old male with Duchenne muscular dystrophy-like features who lost the ability to walk at the age of 11 (Duggan et al. 1997). The variant was not detected among 100 normal chromosomes. It is reported at a frequency of 0.00095 in the South Asian population of the Exome Aggregation Consortium, but this is based on one allele only and in region of poor coverage. Functional studies conducted in HER-911 cells showed that the variant disrupted membrane localization of the protein, although the mislocalization was rescued by kifunesine treatment (Soheili et al. 2012). Based on the evidence, the p.Gln11Glu variant is classified as a variant of unknown significance but suspicious for pathogenicity for beta-sarcoglycanopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Uncertain significance
(Apr 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002511432.1
First in ClinVar: May 16, 2022 Last updated: May 16, 2022 |
Comment:
Variant summary: SGCB c.31C>G (p.Gln11Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: SGCB c.31C>G (p.Gln11Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00023 in 38616 control chromosomes. c.31C>G has been reported in the literature in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (example, Duggan_1997, Soheilli_2012). These data indicate that the variant is likely to be associated with disease. To our knowledge, no quantitative experimental evidence demonstrating an impact on protein function has been reported, although it has been demonstrated to impair membrane localization of Sarcoglycans in vitro (Soheilli_2012). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. (less)
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Uncertain significance
(Oct 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2E
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002601586.1
First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 |
Comment:
A heterozygous missense variation in exon 1 of the SGCB gene that results in the amino acid substitution of Glutamic Acid for Glutamine at codon … (more)
A heterozygous missense variation in exon 1 of the SGCB gene that results in the amino acid substitution of Glutamic Acid for Glutamine at codon 11 (p.Gln11Glu) was detected. This variant c.31C>G (p.Gln11Glu) has not been reported in the 1000 genomes databases. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as uncertain significance. (less)
Age: 10-19 years
Sex: female
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on the Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
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Uncertain significance
(Oct 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2E
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002778014.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Mar 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2E
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000642378.3
First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 11 of the SGCB protein … (more)
This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 11 of the SGCB protein (p.Gln11Glu). This variant is present in population databases (rs752492870, gnomAD 0.1%). This missense change has been observed in individual(s) with muscular dystrophy (PMID: 9032047). ClinVar contains an entry for this variant (Variation ID: 282248). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects SGCB function (PMID: 22095924). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Oct 08, 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: SCV002004040.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
Comment:
Functional analysis of transfected cells showed that Q11E disrupted localization of the SGCB protein to the cell membrane (Soheili et al., 2012); Missense variants in … (more)
Functional analysis of transfected cells showed that Q11E disrupted localization of the SGCB protein to the cell membrane (Soheili et al., 2012); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 9032047, 30564623, 22095924) (less)
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Uncertain significance
(Oct 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2E
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003827602.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Mar 21, 2020)
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no assertion criteria provided
Method: clinical testing
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Limb-girdle muscular dystrophy type 2E
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002082997.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications. | Soheili T | Human mutation | 2012 | PMID: 22095924 |
Mutations in the sarcoglycan genes in patients with myopathy. | Duggan DJ | The New England journal of medicine | 1997 | PMID: 9032047 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCB | - | - | - | - |
Text-mined citations for rs752492870 ...
HelpRecord last updated Mar 17, 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.