ClinVar Genomic variation as it relates to human health
NM_033337.3(CAV3):c.166G>A (p.Gly56Ser)
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_033337.3(CAV3):c.166G>A (p.Gly56Ser)
Variation ID: 8278 Accession: VCV000008278.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.3 3: 8745577 (GRCh38) [ NCBI UCSC ] 3: 8787263 (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 Jun 9, 2014 Feb 20, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_033337.3:c.166G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_203123.1:p.Gly56Ser missense NM_001234.5:c.166G>A NP_001225.1:p.Gly56Ser missense NC_000003.12:g.8745577G>A NC_000003.11:g.8787263G>A NG_008797.2:g.16768G>A LRG_329:g.16768G>A LRG_329t1:c.166G>A LRG_329p1:p.Gly56Ser P56539:p.Gly56Ser - Protein change
- G56S
- Other names
- p.G56S:GGC>AGC
- Canonical SPDI
- NC_000003.12:8745576: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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0.04093 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00888
Exome Aggregation Consortium (ExAC) 0.01073
The Genome Aggregation Database (gnomAD) 0.03558
Trans-Omics for Precision Medicine (TOPMed) 0.03771
1000 Genomes Project 0.04093
1000 Genomes Project 30x 0.04325
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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CAV3 | - | - |
GRCh38 GRCh37 |
100 | 439 | |
OXTR | - | - |
GRCh38 GRCh37 |
25 | 363 |
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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Uncertain significance (1) |
no assertion criteria provided
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Jan 1, 2005 | RCV000008768.16 | |
Benign (9) |
criteria provided, multiple submitters, no conflicts
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Apr 28, 2017 | RCV000039799.40 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Nov 29, 2023 | RCV000119393.25 | |
Benign (1) |
criteria provided, single submitter
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Jun 24, 2013 | RCV000171805.9 | |
Benign (1) |
criteria provided, single submitter
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Jul 16, 2015 | RCV000249765.10 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000362621.13 | |
Likely benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000987086.9 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV001082614.12 | |
Benign (1) |
criteria provided, single submitter
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Jul 31, 2020 | RCV001171080.11 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001150159.12 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 18, 2022 | RCV002496306.8 | |
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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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Benign
(Jun 24, 2013)
|
criteria provided, single submitter
Method: research
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Muscular dystrophy, limb girdle
Affected status: unknown
Allele origin:
unknown
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050817.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015 |
Number of individuals with the variant: 8
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Benign
(-)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000315205.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Limb-Girdle Muscular Dystrophy, Dominant
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000446411.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Benign
(May 10, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000063488.5
First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016 |
Comment:
Gly56Ser in exon 2 of CAV3: This variant is not expected to have clinical signif icance because it has been identified in 10.9% (407/3738) of … (more)
Gly56Ser in exon 2 of CAV3: This variant is not expected to have clinical signif icance because it has been identified in 10.9% (407/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs72546667) (less)
Number of individuals with the variant: 47
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Caveolinopathy
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001311172.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jul 31, 2020)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333750.2
First in ClinVar: May 31, 2020 Last updated: Jan 03, 2022 |
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Benign
(Jul 16, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000318378.6
First in ClinVar: Oct 02, 2016 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Likely benign
(Apr 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Elevated circulating creatine kinase concentration
Hypertrophic cardiomyopathy 1 Rippling muscle disease 2 Long QT syndrome 9 Distal myopathy, Tateyama type
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002808904.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Sep 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000511778.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Benign
(Jul 11, 2011)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000167537.11
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Mar 01, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000114281.8
First in ClinVar: Jan 22, 2014 Last updated: May 30, 2018 |
Number of individuals with the variant: 7
Sex: mixed
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136284.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV000841367.2
First in ClinVar: Mar 08, 2017 Last updated: Jan 26, 2021 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000560127.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024 |
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Benign
(Nov 29, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602912.6
First in ClinVar: Oct 02, 2016 Last updated: Feb 20, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000150542.2
First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014 |
Comment:
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more)
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
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: SCV001959989.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Uncertain significance
(Jan 01, 2005)
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000028977.7
First in ClinVar: Apr 04, 2013 Last updated: Nov 05, 2022 |
Comment on evidence:
This variant, formerly titled MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1C, AUTOSOMAL RECESSIVE, has been reclassified as a variant of unknown significance based on the findings by … (more)
This variant, formerly titled MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1C, AUTOSOMAL RECESSIVE, has been reclassified as a variant of unknown significance based on the findings by de Paula et al. (2001) and Hamosh (2018). Note that Limb-girdle muscular dystrophy (LGMD1C) was reclassified by Straub et al. (2018) as rippling muscle disease (RMD2; 606072). The numbering of this CAV3 mutation (G56S) is based on the numbering system used by Fulizio et al. (2005). Early reports designated this mutation GLY55SER. McNally et al. (1998) found homozygosity for a gly55-to-ser change (G55S) in 1 of 82 patients with muscular dystrophy screened for mutations in the CAV3 gene. This patient was the only affected member of her family, and developed proximal muscle weakness in the first decade. The mutation was not identified in 200 control chromosomes. Expression of dystrophin, the sarcoglycans, and caveolin-3 was grossly normal in a skeletal muscle biopsy from the patient, and the authors suggested that the G55S change may not alter the intracellular location of the protein, yet may interfere with the normal function of the protein in the membrane. Among 61 Brazilian patients diagnosed with LGMD, de Paula et al. (2001) identified 2 patients with a heterozygous G55S mutation. Both patients had onset in adulthood, calf hypertrophy, elevated creatine kinase, and difficulty walking. Muscle protein analyses from both patients were normal. Screening of 200 normal Brazilian chromosomes revealed heterozygosity for the G55S change in 4 subjects and for a C71W change (601253.0004) in 1 subject. The authors concluded that the G55S and C71W changes are rare polymorphisms and do not cause the abnormal phenotype when present in just one allele. The abnormal phenotype in the 2 patients is likely caused by mutation in another LGMD gene. Hamosh (2018) found that the G55S variant was present in heterozygous state in 3,142 of 277,064 alleles and in 184 homozygotes in the gnomAD database (January 24, 2018), calling into question the pathogenicity of the variant. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
|
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: SCV001798728.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001924523.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929363.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
germline
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Leiden Muscular Dystrophy (CAV3)
Accession: SCV000154300.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
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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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229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017. | Straub V | Neuromuscular disorders : NMD | 2018 | PMID: 30055862 |
Molecular and muscle pathology in a series of caveolinopathy patients. | Fulizio L | Human mutation | 2005 | PMID: 15580566 |
Mutations in the caveolin-3 gene: When are they pathogenic? | de Paula F | American journal of medical genetics | 2001 | PMID: 11251997 |
Hamosh, A. Personal Communication. 2018. Baltimore, Md. | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CAV3 | - | - | - | - |
McNally, E. M. Personal Communication. 1998. Chicago, Ill. | - | - | - | - |
Text-mined citations for rs72546667 ...
HelpRecord last updated Apr 15, 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.