ClinVar Genomic variation as it relates to human health
NM_000232.5(SGCB):c.1_2del (p.Met1fs)
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.1_2del (p.Met1fs)
Variation ID: 282860 Accession: VCV000282860.21
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 4q12 4: 52038258-52038259 (GRCh38) [ NCBI UCSC ] 4: 52904424-52904425 (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 Aug 20, 2017 Feb 14, 2024 Dec 30, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000232.5:c.1_2del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000223.1:p.Met1fs frameshift initiator codon variant NM_000232.4:c.1_2delAT NC_000004.12:g.52038258_52038259del NC_000004.11:g.52904424_52904425del NG_008891.1:g.5061_5062del LRG_204:g.5061_5062del - Protein change
- Other names
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- Canonical SPDI
- NC_000004.12:52038257:AT:
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00006
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
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
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 | - | 98 |
SGCB | - | - |
GRCh38 GRCh37 |
495 | 606 |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jul 18, 2018 | RCV000498910.7 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2017 | RCV000778734.4 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 30, 2023 | RCV000812020.12 |
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
(Jul 18, 2018)
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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: SCV000334560.5
First in ClinVar: Dec 06, 2016 Last updated: Sep 03, 2023 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Jun 16, 2017)
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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: SCV000589651.4
First in ClinVar: Aug 20, 2017 Last updated: Sep 03, 2023 |
Comment:
The c.1_2delAT pathogenic variant in the SGCB gene has been reported previously in two unrelated individuals with sacroglycanopathy who also a second pathogenic variant in … (more)
The c.1_2delAT pathogenic variant in the SGCB gene has been reported previously in two unrelated individuals with sacroglycanopathy who also a second pathogenic variant in SGCB identified (Klinge et al., 2008). Immunohistochemistry of muscle biopies from both patients showed reduction of beta, gamma, and delta sarcoglycan (Klinge et al., 2008). The variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Met." (less)
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Likely pathogenic
(Jul 10, 2017)
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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: SCV000915092.2
First in ClinVar: May 27, 2019 Last updated: Sep 03, 2023 |
Comment:
The SGCB c.1_2delAT (p.Met1?) variant has been reported in a single study and was found in a compound heterozygous state with the same missense variant … (more)
The SGCB c.1_2delAT (p.Met1?) variant has been reported in a single study and was found in a compound heterozygous state with the same missense variant in two unrelated individuals with a severe phenotype of beta-sarcoglycanopathy (Klinge et al. 2008). Control data are unavailable for this variant, and it is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or Genome Aggregation Database. However, the coverage of this genomic region may not have been adequate to provide an accurate estimate of the true population frequency. The p.Met1? variant interrupts the initiation codon, and although functional studies of the variant have not been conducted, both compound heterozygous patients showed absent or reduced beta-sarcoglycan expression on immunohistochemistry of muscle biopsies. Based on the evidence, the p.Met1? variant is classified as likely pathogenic 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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Pathogenic
(-)
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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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Baylor Genetics
Accession: SCV001162968.2
First in ClinVar: Feb 28, 2020 Last updated: Sep 03, 2023 |
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Pathogenic
(Oct 26, 2017)
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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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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449906.2
First in ClinVar: Dec 10, 2020 Last updated: Sep 03, 2023 |
Number of individuals with the variant: 2
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Pathogenic
(Apr 28, 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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Revvity Omics, Revvity
Accession: SCV003825623.3
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 30, 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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Invitae
Accession: SCV000952318.7
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects the initiator methionine of the SGCB mRNA. The next in-frame methionine is located at codon 22. The frequency data for this … (more)
This sequence change affects the initiator methionine of the SGCB mRNA. The next in-frame methionine is located at codon 22. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of the initiator codon has been observed in individuals with clinical features of SGCB-related conditions (PMID: 12566530, 15938573, 18996010, 25862795). ClinVar contains an entry for this variant (Variation ID: 282860). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 16, 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: SCV002083004.2
First in ClinVar: Apr 23, 2022 Last updated: Sep 03, 2023 |
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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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Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E. | Semplicini C | Neurology | 2015 | PMID: 25862795 |
Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? | Klinge L | Neuromuscular disorders : NMD | 2008 | PMID: 18996010 |
Beta-sarcoglycan gene mutations in Turkey. | Balci B | Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology | 2004 | PMID: 15938573 |
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 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCB | - | - | - | - |
Text-mined citations for rs886042503 ...
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.