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NM_033337.2(CAV3):c.136G>A (p.Ala46Thr)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Sep 1, 2021)
Last evaluated:
Apr 12, 2021
Accession:
VCV000008281.10
Variation ID:
8281
Description:
single nucleotide variant
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NM_033337.2(CAV3):c.136G>A (p.Ala46Thr)

Allele ID
23320
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.3
Genomic location
3: 8745547 (GRCh38) GRCh38 UCSC
3: 8787233 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_329:g.16738G>A
NC_000003.11:g.8787233G>A
NC_000003.12:g.8745547G>A
... more HGVS
Protein change
A46T
Other names
-
Canonical SPDI
NC_000003.12:8745546:G:A
Functional consequence
functional variant [Sequence Ontology SO:0001536]
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA119428
Leiden Muscular Dystrophy (CAV3): CAV3_00005
UniProtKB: P56539#VAR_011513
OMIM: 601253.0005
dbSNP: rs116840789
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 criteria provided, multiple submitters, no conflicts Apr 12, 2021 RCV000024382.6
Pathogenic 1 criteria provided, single submitter Sep 8, 2020 RCV001384920.1
Pathogenic 1 no assertion criteria provided Jan 1, 2005 RCV000008772.6
Pathogenic 1 no assertion criteria provided Jan 1, 2005 RCV000008774.5
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CAV3 - - GRCh38
GRCh37
197 329

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 07, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000612682.2
Submitted: (Aug 31, 2018)
Evidence details
Publications
PubMed (9)
Pathogenic
(Jan 06, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000704724.2
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Sep 08, 2020)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV001584610.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces alanine with threonine at codon 46 of the CAV3 protein (p.Ala46Thr). The alanine residue is highly conserved and there is a … (more)
Pathogenic
(Apr 12, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001817558.1
Submitted: (Sep 01, 2021)
Evidence details
Comment:
Published functional studies demonstrate a damaging effect (Brauers et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein … (more)
Pathogenic
(Feb 01, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001334695.5
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Jan 01, 2005)
no assertion criteria provided
Method: literature only
RIPPLING MUSCLE DISEASE 2
Allele origin: germline
OMIM
Accession: SCV000028981.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (6)
Pathogenic
(Jan 01, 2005)
no assertion criteria provided
Method: literature only
CREATINE PHOSPHOKINASE, ELEVATED SERUM
Allele origin: germline
OMIM
Accession: SCV000028983.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (6)
not provided
(Apr 15, 2012)
no assertion provided
Method: curation
not specified
Allele origin: de novo, germline
Leiden Muscular Dystrophy (CAV3)
Accession: SCV000045675.1
Submitted: (Apr 15, 2012)
Evidence details

Functional evidence

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Functional consequence Method Result Submitter Supporting information
has functional consequence
Leiden Muscular Dystrophy (CAV3)
Accession: SCV000045675.1
Submitted: (Apr 15, 2012)
Evidence details

Citations for this variant

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Title Author Journal Year Link
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
Mutation in the caveolin-3 gene causes asymmetrical distal myopathy. Chen J Neuropathology : official journal of the Japanese Society of Neuropathology 2016 PMID: 26947586
A family with discordance between malignant hyperthermia susceptibility and rippling muscle disease. Sundblom J Journal of anesthesia 2013 PMID: 22976939
Unilateral calf atrophy secondary to a de novo mutation of the caveolin-3 gene. Arias Gómez M Muscle & nerve 2011 PMID: 21660982
Differential effects of myopathy-associated caveolin-3 mutants on growth factor signaling. Brauers E The American journal of pathology 2010 PMID: 20472890
Bedside diagnosis of rippling muscle disease in CAV3 p.A46T mutation carriers. Sundblom J Muscle & nerve 2010 PMID: 20229577
Caveolinopathy--new mutations and additional symptoms. Aboumousa A Neuromuscular disorders : NMD 2008 PMID: 18583131
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
Molecular and muscle pathology in a series of caveolinopathy patients. Fulizio L Human mutation 2005 PMID: 15580566
Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease. Kubisch C Annals of neurology 2003 PMID: 12666119
Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease. Betz RC Nature genetics 2001 PMID: 11431690
Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy. Herrmann R Human molecular genetics 2000 PMID: 11001938
Phenotypic variability in rippling muscle disease. Vorgerd M Neurology 1999 PMID: 10227634
A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita thomsen. Torbergsen T Acta neurologica Scandinavica 1975 PMID: 1146501
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CAV3 - - - -

Text-mined citations for rs116840789...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2021