Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000530943 | SCV000643191 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2020-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 14809 of the TTN protein (p.Val14809Met). Conservation data is not available for this valine residue. There is a small physicochemical difference between valine and methionine. This variant also falls at the first nucleotide of exon 241 of the TTN coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TTN-related disease. Experimental studies and protein prediction algorithms are not available for this variant, and the functional significance of this missense variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel missense change with uncertain impact on splicing and protein function. It has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002404470 | SCV002714206 | uncertain significance | Cardiovascular phenotype | 2019-07-17 | criteria provided, single submitter | clinical testing | The p.V5744M variant (also known as c.17230G>A), located in coding exon 68 of the TTN gene, results from a G>A substitution at nucleotide position 17230. The valine at codon 5744 is replaced by methionine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 68. The splice prediction software does not produce a reliable prediction for the nearby native splice acceptor site. This amino acid position is well conserved in available vertebrate species. In addition, the amino acid change 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. |
| Fulgent Genetics, |
RCV002476162 | SCV002793731 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2021-07-17 | criteria provided, single submitter | clinical testing |