Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040341 | SCV000064032 | uncertain significance | not specified | 2013-01-22 | criteria provided, single submitter | clinical testing | The Arg15131Pro variant in TTN variant has not been reported in the literature, but has been identified by our laboratory in one child with HCM. This variant ha s also not been identified in large and broad European American and African Amer ican populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington .edu/EVS), though it may be common in other populations. Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg15131Pro variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Another variant at this position ( Arg15131His) has been identified in a small percentage of European American chro mosomes by the NHLBI Exome Sequencing Project, raising the possibility that chan ges at this position would be tolerated. In summary, additional information is n eeded to fully assess the clinical significance of the Arg15131Pro variant. |
| Ambry Genetics | RCV002426578 | SCV002743996 | uncertain significance | Cardiovascular phenotype | 2018-10-24 | criteria provided, single submitter | clinical testing | The p.R8634P variant (also known as c.25901G>C), located in coding exon 104 of the TTN gene, results from a G to C substitution at nucleotide position 25901. The arginine at codon 8634 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |