ClinVar Miner

Submissions for variant NM_003673.4(TCAP):c.316C>T (p.Arg106Cys)

gnomAD frequency: 0.00813  dbSNP: rs45578741
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Total submissions: 21
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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 RCV000172591 SCV000051422 likely benign Primary familial hypertrophic cardiomyopathy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000037793 SCV000061455 benign not specified 2015-05-18 criteria provided, single submitter clinical testing p.Arg106Cys in exon 2 of TCAP: This variant is not expected to have clinical sig nificance because it has been identified in 17.4% (1953/11200) of Latino chromos omes, including 177 homozygotes, by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org/; dbSNP rs45578741). Of note, this variant was initia lly described as disease-causing based on its identification in 2 Caucasian indi viduals with HCM and absence from 400 healthy controls (Perrot 2006, Andersen 20 08).
Eurofins NTD LLC (GA) RCV000037793 SCV000112239 benign not specified 2014-03-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000037793 SCV000153009 benign not specified 2017-04-03 criteria provided, single submitter clinical testing
GeneDx RCV000586561 SCV000171971 benign not provided 2018-11-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24037902, 23299917, 19035361, 27535533, 30847666)
Invitae RCV001082352 SCV000287956 benign Hypertrophic cardiomyopathy 25; Primary familial hypertrophic cardiomyopathy 2021-12-15 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037793 SCV000309778 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000245436 SCV000318085 benign Cardiovascular phenotype 2019-05-13 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000586561 SCV000605337 benign not provided 2021-11-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586561 SCV000698214 likely benign not provided 2017-06-12 criteria provided, single submitter clinical testing Variant summary: The TCAP c.316C>T (p.Arg106Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 3/3 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2260/116004 control chromosomes (178 homozygotes) at a frequency of 0.0194821, which is approximately 779 times the estimated maximal expected allele frequency of a pathogenic TCAP variant (0.000025), suggesting this variant is likely a benign polymorphism. The frequency of this variant is particularly higher in Latino populations (0.1744 in ExAC and 0.1526 in GnomAD). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. This variant was reported in HCM (n=1), DCM (n=2), and familial secundum-type atrial septal defect (n=1); however, causal role of the variant in none of the patients has been established. This variant was found in 2 cases where it was co-occurring with TNNI3 c.433C>T, p.Arg145Trp (pathogenic in our internal database) (Anderson_HM_2008) and 2 cases with sudden unexpected death in infancy, both in European (Danish) population. Taken together, this could be a functional polymorphism or modifier; therefore, this variant was classified as likely benign until further co-segregation and functional studies become available.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770526 SCV000901972 benign Cardiomyopathy 2015-10-16 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001122674 SCV001281420 benign Autosomal recessive limb-girdle muscular dystrophy type 2G 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services,Illumina RCV001122675 SCV001281421 benign Hypertrophic cardiomyopathy 25 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Broad Institute Rare Disease Group, Broad Institute RCV001258227 SCV001435129 benign Hypertrophic cardiomyopathy criteria provided, single submitter research The heterozygous p.Arg106Cys variant in TCAP has been identified in at least 1 Danish individual with hypertrophic cardiomyopathy (PMID: 19035361). This variant is classified as benign for autosomal dominant hypertrophic cardiomyopathy because it has been identified in >17% of Latino chromosomes and 178 total homozygotes by ExAC (http://gnomad.broadinstitute.org/).
Athena Diagnostics Inc RCV000037793 SCV001477044 benign not specified 2019-12-27 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000586561 SCV001742001 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000037793 SCV001922554 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000586561 SCV001932007 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000037793 SCV001953721 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000586561 SCV001966327 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000586561 SCV002037090 likely benign not provided no assertion criteria provided clinical testing

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