ClinVar Genomic variation as it relates to human health
NM_000023.4(SGCA):c.101G>A (p.Arg34His)
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_000023.4(SGCA):c.101G>A (p.Arg34His)
Variation ID: 92301 Accession: VCV000092301.60
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.33 17: 50167431 (GRCh38) [ NCBI UCSC ] 17: 48244792 (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 Mar 29, 2015 Apr 15, 2024 Mar 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000023.4:c.101G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000014.1:p.Arg34His missense NM_000023.3:c.101G>A NM_001135697.3:c.101G>A NP_001129169.1:p.Arg34His missense NR_135553.2:n.137G>A non-coding transcript variant NC_000017.11:g.50167431G>A NC_000017.10:g.48244792G>A NG_008889.1:g.6427G>A LRG_203:g.6427G>A LRG_203t1:c.101G>A LRG_203p1:p.Arg34His Q16586:p.Arg34His - Protein change
- R34H
- Other names
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- Canonical SPDI
- NC_000017.11:50167430: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.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
1000 Genomes Project 30x 0.00016
Trans-Omics for Precision Medicine (TOPMed) 0.00002
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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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SGCA | - | - |
GRCh38 GRCh37 |
734 | 757 |
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 (6) |
criteria provided, multiple submitters, no conflicts
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Dec 5, 2022 | RCV000077936.39 | |
Pathogenic (10) |
criteria provided, multiple submitters, no conflicts
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Mar 17, 2024 | RCV000169164.39 |
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
(Jan 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy, limb-girdle, type 2D
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000248859.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(May 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: yes
Allele origin:
unknown
|
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV001251763.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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Pathogenic
(Jun 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001522473.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Jul 27, 2021)
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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 Inc
Accession: SCV002771370.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant was shown to interfere with membrane localization of the protein (PMID 22095924). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. (less)
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Pathogenic
(Feb 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV003921043.1
First in ClinVar: May 06, 2023 Last updated: May 06, 2023 |
Comment:
This variant was identified as homozygous._x000D_ Criteria applied: PS3, PM5_STR, PM3, PM2_SUP
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Pathogenic
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV003931630.1
First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023 |
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Pathogenic
(Feb 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002020091.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001220242.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 34 of the SGCA protein (p.Arg34His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 34 of the SGCA protein (p.Arg34His). This variant is present in population databases (rs371675217, gnomAD 0.006%). This missense change has been observed in individuals with limb-girdle muscular dystrophy (PMID: 7663524, 9032047, 26944168). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 92301). 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 expected to disrupt SGCA protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SGCA function (PMID: 22095924). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 17, 2024)
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criteria provided, single submitter
Method: research
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004804692.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(May 01, 2020)
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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: SCV001334655.19
First in ClinVar: Jun 08, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Dec 15, 2015)
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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: SCV000226997.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 4
Sex: mixed
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Pathogenic
(Dec 05, 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: SCV000616876.3
First in ClinVar: Dec 19, 2017 Last updated: Feb 07, 2023 |
Comment:
Published functional studies demonstrate defective intracellular trafficking of the sarcoglycan proteins (Soheili et al., 2012); In silico analysis supports that this missense variant does not … (more)
Published functional studies demonstrate defective intracellular trafficking of the sarcoglycan proteins (Soheili et al., 2012); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 9153448, 7663524, 9032047, 9192266, 18285821, 22095924, 30919934, 31130284, 31127727, 31589614, 19781108) (less)
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Pathogenic
(Jul 21, 2016)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220392.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 23, 2019 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954314.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Jul 14, 2020)
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no assertion criteria provided
Method: clinical testing
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Limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002087546.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798765.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 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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Elucidation of the Genetic Cause in Dutch Limb Girdle Muscular Dystrophy Families: A 27-Year's Journey. | Ten Dam L | Journal of neuromuscular diseases | 2021 | PMID: 33386810 |
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. | Monies D | American journal of human genetics | 2019 | PMID: 31130284 |
Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service. | Westra D | Journal of neuromuscular diseases | 2019 | PMID: 31127727 |
Identification of thiostrepton as a pharmacological approach to rescue misfolded alpha-sarcoglycan mutant proteins from degradation. | Hoch L | Scientific reports | 2019 | PMID: 31061434 |
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 |
Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients. | Xie Z | Orphanet journal of rare diseases | 2019 | PMID: 30764848 |
Childhood onset limb-girdle muscular dystrophies in the Aegean part of Turkey. | Yiş U | Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology | 2018 | PMID: 30838351 |
LGMD2E is the most common type of sarcoglycanopathies in the Iranian population. | Alavi A | Journal of neurogenetics | 2017 | PMID: 28687063 |
Probable high prevalence of limb-girdle muscular dystrophy type 2D in Taiwan. | Liang WC | Journal of the neurological sciences | 2016 | PMID: 26944168 |
Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications. | Soheili T | Human mutation | 2012 | PMID: 22095924 |
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 |
Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions. | Crosbie RH | Human molecular genetics | 2000 | PMID: 10942431 |
Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D). | Carrié A | Journal of medical genetics | 1997 | PMID: 9192266 |
Primary adhalinopathy (alpha-sarcoglycanopathy): clinical, pathologic, and genetic correlation in 20 patients with autosomal recessive muscular dystrophy. | Eymard B | Neurology | 1997 | PMID: 9153448 |
Mutations in the sarcoglycan genes in patients with myopathy. | Duggan DJ | The New England journal of medicine | 1997 | PMID: 9032047 |
Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity. | Piccolo F | Nature genetics | 1995 | PMID: 7663524 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCA | - | - | - | - |
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Text-mined citations for rs371675217 ...
HelpRecord last updated Apr 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.