Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000461261 | SCV000542331 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-05-14 | criteria provided, single submitter | clinical testing | In summary, this truncating variant is found in the I-band of the TTN protein where truncating variants have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739, 25589632). However, truncating variants in the I-band have been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). For these reasons it has been classified as a Variant of Uncertain Significance. While this variant is present in population databases (rs761617432), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a TTN-related disease. This sequence change deletes 1 nucleotide from exon 197 of the TTN mRNA (c.38660delA), causing a frameshift at codon 12887. This creates a premature translational stop signal in exon 197 of the TTN mRNA (p.Lys12887Argfs*60). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated TTN protein. |
| Athena Diagnostics | RCV000714024 | SCV000844687 | uncertain significance | not provided | 2017-10-18 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002481370 | SCV002782697 | 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 | 2021-10-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000714024 | SCV003927499 | pathogenic | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Located in a region of TTN in which the majority of pathogenic variants have been reported in association with autosomal recessive titinopathies (Fernandez-Marmiesse et al., 2017; Chervinsky et al., 2018; Bryen, et al., 2020; Savarese et al., 2020); Identified in patients with arthrogryposis who have additional TTN variants, though it is unclear if the variants were confirmed to be on opposite alleles (in trans) in each patient (Ravenscroft et al., 2020); This variant is associated with the following publications: (PMID: 33820833, 35580751, 28040389, 29575618, 31660661, 32778822, 33060286) |