ClinVar Genomic variation as it relates to human health
NM_000232.5(SGCB):c.341C>T (p.Ser114Phe)
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.341C>T (p.Ser114Phe)
Variation ID: 42035 Accession: VCV000042035.48
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q12 4: 52029766 (GRCh38) [ NCBI UCSC ] 4: 52895932 (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 Oct 19, 2015 Aug 4, 2024 May 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000232.5:c.341C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000223.1:p.Ser114Phe missense NC_000004.12:g.52029766G>A NC_000004.11:g.52895932G>A NG_008891.1:g.13554C>T LRG_204:g.13554C>T LRG_204t1:c.341C>T Q16585:p.Ser114Phe - Protein change
- Other names
- NM_000232.4(SGCB):c.341C>T(p.Ser114Phe)
- Canonical SPDI
- NC_000004.12:52029765:G:A
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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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD) 0.00019
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00020
Exome Aggregation Consortium (ExAC) 0.00023
The Genome Aggregation Database (gnomAD), exomes 0.00028
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
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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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/Likely pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2024 | RCV000177020.37 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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May 1, 2024 | RCV000271872.33 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 25, 2016 | RCV000340831.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 7, 2014 | RCV001267013.10 |
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
(Mar 05, 2015)
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criteria provided, single submitter
Method: clinical testing
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Limb-girdle muscular dystrophy, type 2E
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000255839.2
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015 |
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Pathogenic
(Jul 05, 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: SCV000228827.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 25
Sex: mixed
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Pathogenic
(Sep 25, 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: SCV000449671.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The SGCB c.341C>T (p.Ser114Phe) missense variant has been reported in at least five studies in which it has been identified in a homozygous state in … (more)
The SGCB c.341C>T (p.Ser114Phe) missense variant has been reported in at least five studies in which it has been identified in a homozygous state in eight individuals with sarcoglycanopathy, in a compound heterozygous state in three affected individuals, and in a heterozygous state in two affected individuals in whom a second variant was not identified (Duggan et al. 1997; Crosbie et al. 2000; Trabelsi et al. 2008; Klinge et al. 2008; Wong-Kisiel et al. 2010). The p.Ser114Phe variant was absent from 50 controls and is reported at a frequency of 0.00047 in the European-American population of the Exome Sequencing Project. Transfection of the p.Ser114Phe variant into HER-911 cells demonstrated accumulation of the protein in the endoplasmic reticulum, indicating the variant disrupts transport of the protein to the cell surface (Soheili et al. 2011). Based on the evidence, the p.Ser114Phe variant is classified as 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
(Feb 18, 2022)
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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: SCV000329935.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Published functional studies indicate S114F results in defective intracellular trafficking of sarcoglycan proteins (Sohelli et al., 2012); Missense variants in this gene are often considered … (more)
Published functional studies indicate S114F results in defective intracellular trafficking of sarcoglycan proteins (Sohelli et al., 2012); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23349452, 17994539, 10942431, 20071171, 18996010, 27447704, 26990548, 22095924, 15032976, 10993494, 18285821, 30564623, 30919934, 9032047, 31980526, 31589614, 32528171, 33726816, 8968749) (less)
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Pathogenic
(Mar 25, 2024)
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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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Baylor Genetics
Accession: SCV004208733.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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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 2E
(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: SCV001164541.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
Comment:
The homozygous p.Ser114Phe variant in SGCB was identified by our study in one individual with limb-girdle muscular dystrophy (LGMD). This variant has been identified in … (more)
The homozygous p.Ser114Phe variant in SGCB was identified by our study in one individual with limb-girdle muscular dystrophy (LGMD). This variant has been identified in 0.02706% (75/277202) of chromosomes in the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs150518260). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The p.Ser114Phe variant in SGCB has been reported in more than 62 individuals with Limb-Girdle Muscular Dystrophy in the homozygous and heterozygous state (PMID: 22095924, 25862795, 25135358). The presence of this variant in combination with many other possibly pathogenic variants and in individuals with LGMD increases the likelihood that the p.Ser114Phe variant is pathogenic. In vitro functional studies provide some evidence that the p.Ser114Phe variant may impact protein function by impairing membrane localization (PMID: 22095924). This variant has also been reported pathogenic in ClinVar by multiple submitters (Variation ID: 42035). In summary, the clinical significance of the p.Ser114Phe variant is pathogenic. ACMG/AMP Criteria applied: PM2, PP3, PS3, PM3_Strong (Richards 2015). (less)
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Pathogenic
(Nov 11, 2019)
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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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Myriad Genetics, Inc.
Accession: SCV001193983.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_000232.4(SGCB):c.341C>T(S114F) is classified as pathogenic in the context of beta-sarcoglycanopathy. Sources cited for classification include the following: PMID 22095924, 10993494, 10942431, 18285821, 9032047, and 18996010. … (more)
NM_000232.4(SGCB):c.341C>T(S114F) is classified as pathogenic in the context of beta-sarcoglycanopathy. Sources cited for classification include the following: PMID 22095924, 10993494, 10942431, 18285821, 9032047, and 18996010. Classification of NM_000232.4(SGCB):c.341C>T(S114F) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446819.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Muscular dystrophy (present)
Sex: male
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Pathogenic
(Jun 28, 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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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501573.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(Sep 07, 2014)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001445194.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Jul 13, 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: SCV002020106.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 22, 2024)
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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: SCV000642379.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 114 of the SGCB protein (p.Ser114Phe). … (more)
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 114 of the SGCB protein (p.Ser114Phe). This variant is present in population databases (rs150518260, gnomAD 0.05%). This missense change has been observed in individuals with limb-girdle muscular dystrophy (PMID: 9032047, 10942431, 18285821, 20071171, 23349452, 25135358, 25862795, 26404900). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 42035). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SGCB protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects SGCB function (PMID: 22095924). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(May 31, 2018)
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criteria provided, single submitter
Method: curation
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Autosomal recessive limb-girdle muscular dystrophy type 2E
Affected status: unknown
Allele origin:
unknown
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SIB Swiss Institute of Bioinformatics
Accession: SCV000803527.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
This variant is interpreted as a Likely Pathogenic, for Muscular dystrophy, limb-girdle, type 2E, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 … (more)
This variant is interpreted as a Likely Pathogenic, for Muscular dystrophy, limb-girdle, type 2E, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2-Supporting => PM2 downgraded in strength to Supporting. PS4-Supporting => Recurrent mutation observed in multiple unrelated patients. (PMID:9032047,20071171,18285821,25135358,25862795). PS3 => Well-established functional studies show a deleterious effect (PMID:22095924). (less)
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Likely 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: SCV001449905.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 2
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Pathogenic
(May 01, 2024)
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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: SCV002563816.14
First in ClinVar: Aug 23, 2022 Last updated: Aug 04, 2024 |
Comment:
SGCB: PM3:Very Strong, PM2, PP3, PS3:Supporting
Number of individuals with the variant: 2
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Pathogenic
(Oct 29, 2014)
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no assertion criteria provided
Method: curation
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Autosomal recessive limb-girdle muscular dystrophy type 2E
Affected status: unknown
Allele origin:
germline
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: CSER_ClinSeq
Accession: SCV001132529.1 First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
Secondary finding: yes
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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 2E
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001460963.1
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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Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness. | Töpf A | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32528171 |
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. | Hou YC | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31980526 |
Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients. | Ten Dam L | Clinical genetics | 2019 | PMID: 30919934 |
Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients. | Nallamilli BRR | Annals of clinical and translational neurology | 2018 | PMID: 30564623 |
NGS-Based Assay for the Identification of Individuals Carrying Recessive Genetic Mutations in Reproductive Medicine. | Abulí A | Human mutation | 2016 | PMID: 26990548 |
ISPD mutations account for a small proportion of Italian Limb Girdle Muscular Dystrophy cases. | Magri F | BMC neurology | 2015 | PMID: 26404900 |
Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E. | Semplicini C | Neurology | 2015 | PMID: 25862795 |
Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic. | Stehlíková K | BMC neurology | 2014 | PMID: 25135358 |
Genetic analysis in 418 index patients with idiopathic dilated cardiomyopathy: overview of 10 years' experience. | van Spaendonck-Zwarts KY | European journal of heart failure | 2013 | PMID: 23349452 |
Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications. | Soheili T | Human mutation | 2012 | PMID: 22095924 |
Two siblings with limb-girdle muscular dystrophy type 2E responsive to deflazacort. | Wong-Kisiel LC | Neuromuscular disorders : NMD | 2010 | PMID: 20071171 |
Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? | Klinge L | Neuromuscular disorders : NMD | 2008 | PMID: 18996010 |
Revised spectrum of mutations in sarcoglycanopathies. | Trabelsi M | European journal of human genetics : EJHG | 2008 | PMID: 18285821 |
Sarcoglycanopathies in Dutch patients with autosomal recessive limb girdle muscular dystrophy. | Ginjaar HB | Journal of neurology | 2000 | PMID: 10993494 |
Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions. | Crosbie RH | Human molecular genetics | 2000 | PMID: 10942431 |
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 | - | - | - | - |
http://www.lovd.nl/SGCB | - | - | - | - |
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Text-mined citations for rs150518260 ...
HelpRecord last updated Aug 04, 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.