Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156145 | SCV000205860 | uncertain significance | not specified | 2013-10-03 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Val9527Met variant in TTN has not been previously reported in individuals with cardiomyopat hy, in large population studies, or been observed in our laboratory. This varian t is located in the last base of the exon, which is part of the 5? splice region . Computational tools do predict altered splicing which may lead leading to an a bnormal or absent protein. However, this information is not predictive enough to conclusively determine pathogenicity. Splice and other truncating variants in T TN are strongly associated with DCM and the majority occur in the A-band (Herman 2012, LMM unpublished data); this variant occurs in the I-band. Although this d ata is supportive of pathogenicity for the Val9527Met variant, additional studie s are needed to fully assess its clinical significance. |
| Invitae | RCV001359065 | SCV001554926 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2020-09-20 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. 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. This variant is located in the I band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). This variant has not been reported in the literature in individuals with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 179356). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 10771 of the TTN protein (p.Val10771Met). There is a small physicochemical difference between valine and methionine. This variant also falls at the last nucleotide of exon 127 of the TTN coding sequence, which is part of the consensus splice site for this exon. |
| Fulgent Genetics, |
RCV002498763 | SCV002779906 | 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 | 2021-07-08 | criteria provided, single submitter | clinical testing | |
| CHEO Genetics Diagnostic Laboratory, |
RCV003149953 | SCV003838627 | uncertain significance | Cardiomyopathy | 2021-11-26 | criteria provided, single submitter | clinical testing |