Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000184523 | SCV000237173 | uncertain significance | not provided | 2018-01-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TTN gene. The c.39281 A>G (N13094S) variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.39281 A>G variant is located within exon 189 of the TTN gene and may be functionally significant at protein and/or mRNA level. At the protein level, c.39281 A>G results in the N13094S conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. At the mRNA level, in silico splice prediction programs predict that c.39281 A>G may affect splicing by creating a cryptic splice acceptor site downstream of the natural splice acceptor site in intron 188. Nevertheless, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. Furthermore, the majority of pathogenic variants reported in association with DCM are truncating variants in the A-band region of titin (Herman et al., 2012), while the clinical significance of variants in the I-band, where c.39281 A>G occurs, is not well characterized. Finally, truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012). |
| Fulgent Genetics, |
RCV002478636 | SCV002786346 | 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 | 2021-10-17 | criteria provided, single submitter | clinical testing |