ClinVar Miner

Submissions for variant NM_003673.4(TCAP):c.209G>A (p.Arg70Gln)

gnomAD frequency: 0.00012  dbSNP: rs552865793
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183928 SCV000236416 uncertain significance not provided 2024-07-09 criteria provided, single submitter clinical testing Has not been reported in the literature in individuals with cardiac disease, to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 16490376)
Eurofins Ntd Llc (ga) RCV000183928 SCV000341583 uncertain significance not provided 2016-04-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000793752 SCV000933121 uncertain significance Hypertrophic cardiomyopathy 25; Primary familial hypertrophic cardiomyopathy 2023-10-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 70 of the TCAP protein (p.Arg70Gln). This variant is present in population databases (rs552865793, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TCAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 202110). 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.
Fulgent Genetics, Fulgent Genetics RCV002478630 SCV002775503 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2G; Hypertrophic cardiomyopathy 25 2021-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV004020237 SCV003584659 uncertain significance Cardiovascular phenotype 2023-01-17 criteria provided, single submitter clinical testing The p.R70Q variant (also known as c.209G>A), located in coding exon 2 of the TCAP gene, results from a G to A substitution at nucleotide position 209. The arginine at codon 70 is replaced by glutamine, an amino acid with highly similar properties. 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.
Revvity Omics, Revvity RCV000183928 SCV003827087 uncertain significance not provided 2023-08-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479049 SCV004223454 uncertain significance not specified 2023-11-07 criteria provided, single submitter clinical testing Variant summary: TCAP c.209G>A (p.Arg70Gln) results in a 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 2.1e-05 in 239030 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.209G>A has been reported in the literature in at least one individual affected with noncompaction cardiomyopathy (vanWaning_2018) as well as individuals with clinically suspected-Limb-girdle muscular dystrophies (Nallamilli_2018), however without strong evidence for causality (e.g., lack of co-segregation data). These reports therefore do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29447731, 30564623). Six submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000183928 SCV001744159 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000183928 SCV001957610 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.