ClinVar Miner

Submissions for variant NM_033337.2(CAV3):c.216C>G (p.Cys72Trp) (rs116840776)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171752 SCV000050766 likely benign Limb-girdle muscular dystrophy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150236 SCV000197226 benign not specified 2018-04-09 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000150236 SCV000227543 benign not specified 2014-07-07 criteria provided, single submitter clinical testing
Invitae RCV001084478 SCV000261574 likely benign Long QT syndrome 2020-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000249612 SCV000317954 likely benign Cardiovascular phenotype 2018-09-07 criteria provided, single submitter clinical testing No disease association in small case-control study;Other strong data supporting benign classification
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000150236 SCV000740557 likely benign not specified 2016-12-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282110 SCV000885143 likely benign none provided 2020-02-12 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769171 SCV000900546 benign Cardiomyopathy 2018-08-02 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000769171 SCV000995703 likely benign Cardiomyopathy 2019-03-18 criteria provided, single submitter clinical testing
Mendelics RCV000987087 SCV001136285 uncertain significance Long QT syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000024381 SCV001153761 uncertain significance not provided 2018-09-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001144018 SCV001304592 uncertain significance Caveolinopathy 2017-04-27 criteria provided, single submitter clinical testing 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000150236 SCV001426790 likely benign not specified 2020-07-13 criteria provided, single submitter clinical testing Variant summary: CAV3 c.216C>G (p.Cys72Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 283742 control chromosomes, predominantly at a frequency of 0.0023 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 230 fold of the estimated maximal expected allele frequency for a pathogenic variant in CAV3 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.216C>G has been reported in the literature in individuals with Muscular dystrophy, Long QT syndrome, Sudden Arrhythmic Death Syndrome, Dilated cardiomyopathy or Hypertrophic cardiomyopathy (McNally_1998, Arnestad_2007, Vatta_2006, Pugh_2014, Nunn_2015, Rubattu_2016, Sanchez_2016, Minoche_2018). These reports do not provide unequivocal conclusions about association of the variant with Arrhythmia. In addition, co-occurrences with other pathogenic variants have been reported (MYBPC3 c.1483C>T, p.Arg495Trp; TTN c.69491_69492del, p.Val23164fs) (Rubattu_2016, Minoche_2018), providing supporting evidence for a benign role. At least one publication reports this variant has no impact on protein function (Cai_2009). Ten ClinVar submitters (evaluation after 2014) cites the variant as uncertain significance (3x), likely benign (5x) and benign (2x). Based on the evidence outlined above, the variant was classified as likely benign.
Athena Diagnostics Inc RCV000150236 SCV001477112 benign not specified 2019-12-23 criteria provided, single submitter clinical testing
GeneDx RCV000024381 SCV001887388 benign not provided 2018-11-28 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25630502, 31043699, 27600940, 25783436, 9536092, 23465283, 11251997)
OMIM RCV000008769 SCV000028978 pathogenic Rippling muscle disease 2 2005-01-01 no assertion criteria provided literature only
Leiden Muscular Dystrophy (CAV3) RCV000024381 SCV000045674 not provided not provided 2012-04-15 no assertion provided curation
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477819 SCV000536872 uncertain significance Elevated serum creatine phosphokinase; Familial hypertrophic cardiomyopathy 1; Long QT syndrome 9; Rippling muscle disease 2; Distal myopathy, Tateyama type 2016-03-16 no assertion criteria provided research

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