Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000213316 | SCV000237809 | uncertain significance | not specified | 2014-09-03 | criteria provided, single submitter | clinical testing | Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM-CRDM panel(s). |
Laboratory for Molecular Medicine, |
RCV000213316 | SCV000272803 | uncertain significance | not specified | 2015-03-06 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Asn29273Asp v ariant in TTN has not been previously reported in individuals with cardiomyopath y or large population studies. Asparagine (Asp) at position 29273 is not conserv ed in mammals or evolutionarily distant species with multiple birds having an as partic acid (Asp), which suggests that this change may be tolerated. Other compu tational prediction tools do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Asn29273As p variant is uncertain, the presence of the variant amino acid in multiple other species suggests that it is more likely to be benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769877 | SCV000901303 | uncertain significance | Cardiomyopathy | 2017-06-09 | criteria provided, single submitter | clinical testing |