Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000152521 | SCV000201709 | uncertain significance | not specified | 2013-12-26 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Val695Ala varia nt in TTN has not been reported in individuals with cardiomyopathy and data from large population studies is insufficient to assess the frequency of this varian t. Valine (Val) at position 695 is not conserved in mammals or across evolutiona rily distant species, and several other mammals have an alanine (Ala) at this po sition, suggesting that this change can be tolerated. Computational analyses (bi ochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) s uggest that the Val695Ala variant may not impact the protein, though this inform ation is not predictive enough to rule out pathogenicity. Although this data sup ports that the Val695Ala variant may be benign, additional studies are needed to fully assess its clinical significance. |
| Ambry Genetics | RCV002408677 | SCV002723988 | uncertain significance | Cardiovascular phenotype | 2018-12-05 | criteria provided, single submitter | clinical testing | The p.V649A variant (also known as c.1946T>C), located in coding exon 12 of the TTN gene, results from a T to C substitution at nucleotide position 1946. The valine at codon 649 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other 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. |