ClinVar Genomic variation as it relates to human health
NM_000070.3(CAPN3):c.598_612del (p.Phe200_Leu204del)
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_000070.3(CAPN3):c.598_612del (p.Phe200_Leu204del)
Variation ID: 166786 Accession: VCV000166786.42
- Type and length
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Deletion, 15 bp
- Location
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Cytogenetic: 15q15.1 15: 42387851-42387865 (GRCh38) [ NCBI UCSC ] 15: 42680049-42680063 (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 19, 2017 May 12, 2024 Jan 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000070.3:c.598_612del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000061.1:p.Phe200_Leu204del inframe deletion NM_000070.3:c.598_612delTTCTGGAGTGCTCTG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_024344.2:c.598_612del NP_077320.1:p.Phe200_Leu204del inframe deletion NM_173087.2:c.598_612del NP_775110.1:p.Phe200_Leu204del inframe deletion NC_000015.10:g.42387852_42387866del NC_000015.9:g.42680050_42680064del NG_008660.1:g.44750_44764del LRG_849:g.44750_44764del LRG_849t1:c.598_612del LRG_849p1:p.Phe200_Leu204del - Protein change
- Other names
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- Canonical SPDI
- NC_000015.10:42387850:GTTCTGGAGTGCTCTG:G
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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.
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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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CAPN3 | - | - |
GRCh38 GRCh37 |
1700 | 1839 |
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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Jan 16, 2024 | RCV000152920.18 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2023 | RCV000516177.32 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 5, 2023 | RCV003474804.1 |
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
(Jan 25, 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
Accession: SCV000255669.4
First in ClinVar: Oct 19, 2015 Last updated: Sep 19, 2021 |
Comment:
This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls (http://gnomad.broadinstitute.org). In multiple individuals, this variant has been … (more)
This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls (http://gnomad.broadinstitute.org). 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
(Oct 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy, limb-girdle, autosomal dominant 4
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211546.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 25, 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: SCV000202348.7
First in ClinVar: Jan 31, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 23
Sex: mixed
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Pathogenic
(Oct 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2A
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581151.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS1, PS4_MOD, PM2_SUP_MOD, PM3, PM4
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Number of individuals with the variant: 2
Sex: female
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Pathogenic
(Sep 10, 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: SCV000709910.3
First in ClinVar: Apr 02, 2018 Last updated: May 27, 2023 |
Comment:
In-frame deletion of 5 amino acids in a non-repeat region predicted to critically alter the protein; In silico analysis supports a deleterious effect on protein … (more)
In-frame deletion of 5 amino acids in a non-repeat region predicted to critically alter the protein; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15733273, 15221789, 16141003, 34720847, 34863162, 30919934, 31589614, 32528171, 9452114, 33107701, 27447704, 16372320, 17236769, 10330340, 10679950, 14981715, 17994539, 15351423, 25135358, 17157502, 34426522, 16100770) (less)
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Pathogenic
(Feb 11, 2022)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004223990.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP1, PP4_moderate, PM2, PM3_strong, PM4, PS4_moderate
Number of individuals with the variant: 1
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Pathogenic
(Nov 14, 2019)
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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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Revvity Omics, Revvity
Accession: SCV002018054.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2A
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000645507.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This variant, c.598_612del, results in the deletion of 5 amino acid(s) of the CAPN3 protein (p.Phe200_Leu204del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.598_612del, results in the deletion of 5 amino acid(s) of the CAPN3 protein (p.Phe200_Leu204del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs771137354, gnomAD 0.005%). This variant has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 9452114, 16141003, 18854869, 25135358). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported in individual(s) with autosomal dominant limb-girdle muscular dystrophy (PMID: 15733273); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 166786). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 01, 2023)
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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: SCV001246428.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
CAPN3: PM3:Very Strong, PM2, PM4
Number of individuals with the variant: 5
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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 2A
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001461313.1
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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The genetic structure of the Turkish population reveals high levels of variation and admixture. | Kars ME | Proceedings of the National Academy of Sciences of the United States of America | 2021 | PMID: 34426522 |
Autosomal dominant segregation of CAPN3 c.598_612del15 associated with a mild form of calpainopathy. | Cerino M | Annals of clinical and translational neurology | 2020 | PMID: 33107701 |
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 |
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. | Capalbo A | PLoS genetics | 2019 | PMID: 31589614 |
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 |
Muscular dystrophies and myopathies: the spectrum of mutated genes in the Czech Republic. | Stehlíková K | Clinical genetics | 2017 | PMID: 27447704 |
MicroRNA signatures predict dysregulated vitamin D receptor and calcium pathways status in limb girdle muscle dystrophies (LGMD) 2A/2B. | Aguennouz M | Cell biochemistry and function | 2016 | PMID: 27558075 |
A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. | Vissing J | Brain : a journal of neurology | 2016 | PMID: 27259757 |
Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic. | Stehlíková K | BMC neurology | 2014 | PMID: 25135358 |
How to tackle the diagnosis of limb-girdle muscular dystrophy 2A. | Fanin M | European journal of human genetics : EJHG | 2009 | PMID: 18854869 |
Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients. | Guglieri M | Human mutation | 2008 | PMID: 17994539 |
Quantitative analysis of CAPN3 transcripts in LGMD2A patients: involvement of nonsense-mediated mRNA decay. | Stehlíková K | Neuromuscular disorders : NMD | 2007 | PMID: 17157502 |
Analysis of histopathologic and molecular pathologic findings in Czech LGMD2A patients. | Hermanová M | Muscle & nerve | 2006 | PMID: 16372320 |
Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes. | Piluso G | Journal of medical genetics | 2005 | PMID: 16141003 |
Novel mutations in the calpain 3 gene in Germany. | Todorova A | Clinical genetics | 2005 | PMID: 15733273 |
High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia. | Pogoda TV | Human mutation | 2000 | PMID: 10679950 |
A small in-frame deletion within the protease domain of muscle-specific calpain, p94 causes early-onset limb-girdle muscular dystrophy 2A. | Häffner K | Human mutation | 1998 | PMID: 9452114 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CAPN3 | - | - | - | - |
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Text-mined citations for rs727503837 ...
HelpRecord last updated May 12, 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.