Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000412896 | SCV000492118 | uncertain significance | not specified | 2016-11-28 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TTN gene. The I17641V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I17641V variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I17641V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to isoleucine, including valine, are tolerated across species. Additionally, the adenine nucleotide at this coding position is not conserved across species, where guanine is wild type in at least one other species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Ambry Genetics | RCV002446636 | SCV002753691 | uncertain significance | Cardiovascular phenotype | 2019-06-27 | criteria provided, single submitter | clinical testing | The p.I10217V variant (also known as c.30649A>G), located in coding exon 122 of the TTN gene, results from an A to G substitution at nucleotide position 30649. The isoleucine at codon 10217 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, valine 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. |
Revvity Omics, |
RCV003137997 | SCV003821679 | uncertain significance | not provided | 2019-02-05 | criteria provided, single submitter | clinical testing |