Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489775 | SCV000577382 | uncertain significance | not provided | 2017-03-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TCAP gene. The R33Q variant has not been published as pathogenic or been reported as benign to our knowledge. Additionally, this variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R33Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Lastly, this substitution occurs at a position that is conserved in mammals, however, glutamine (Q) is the wild-type residue at this position in at least two non-mammalian species. |
| Labcorp Genetics |
RCV001342904 | SCV001536854 | uncertain significance | Hypertrophic cardiomyopathy 25; Primary familial hypertrophic cardiomyopathy | 2024-11-25 | 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 33 of the TCAP protein (p.Arg33Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 426834). 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, |
RCV002489196 | SCV002800189 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2G; Hypertrophic cardiomyopathy 25 | 2021-09-17 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003302725 | SCV004000858 | uncertain significance | Cardiovascular phenotype | 2023-03-20 | criteria provided, single submitter | clinical testing | The p.R33Q variant (also known as c.98G>A), located in coding exon 1 of the TCAP gene, results from a G to A substitution at nucleotide position 98. The arginine at codon 33 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |