ClinVar Miner

Submissions for variant NM_003673.4(TCAP):c.208C>T (p.Arg70Trp)

gnomAD frequency: 0.00003  dbSNP: rs775636212
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172108 SCV000051051 uncertain significance Hypertrophic cardiomyopathy 2013-06-24 criteria provided, single submitter research
Eurofins Ntd Llc (ga) RCV000382675 SCV000338466 uncertain significance not provided 2016-01-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000536183 SCV000639695 uncertain significance Hypertrophic cardiomyopathy 25; Primary familial hypertrophic cardiomyopathy 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 70 of the TCAP protein (p.Arg70Trp). This variant is present in population databases (rs775636212, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of hypertrophic cardiomyopathy and/or dilated cardiomyopathy (PMID: 17097056, 32880476; Invitae). ClinVar contains an entry for this variant (Variation ID: 189789). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV000382675 SCV001151280 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002505226 SCV002817033 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2G; Hypertrophic cardiomyopathy 25 2021-09-25 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000382675 SCV003827079 uncertain significance not provided 2020-08-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV003162725 SCV003860754 uncertain significance Cardiovascular phenotype 2023-02-27 criteria provided, single submitter clinical testing The p.R70W variant (also known as c.208C>T), located in coding exon 2 of the TCAP gene, results from a C to T substitution at nucleotide position 208. The arginine at codon 70 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was detected in the homozygous state (along with other homozygous variants) in a patient with complex congenital heart defect, ambiguous genitalia, and mild limb hypotonia (Mazen I et al. Sex Dev, 2016 Apr;10:16-22). This variant has also been detected in the heterozygous state in cohorts with cardiomyopathy or arrhythmia (Theis JL et al. Biochem Biophys Res Commun, 2006 Dec;351:896-902; Blom LJ et al. Europace, 2019 Oct;21:1519-1526; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 Oct;13:476-487; Ware SM et al. Am J Hum Genet, 2022 Feb;109:282-298). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV000382675 SCV005198758 uncertain significance not provided 2023-04-06 criteria provided, single submitter clinical testing
OMIM RCV000170303 SCV000222651 pathogenic Hypertrophic cardiomyopathy 25 2006-12-29 no assertion criteria provided literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000382675 SCV001977833 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000382675 SCV001978996 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000382675 SCV001979727 uncertain significance not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.