Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001810601 | SCV001474342 | uncertain significance | not provided | 2020-06-30 | criteria provided, single submitter | clinical testing | The TTN c.33791C>T; p.Pro11264Leu variant (rs1336824666) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Pro11264Leu variant cannot be determined with certainty. Pathogenic variants in the TTN gene are inherited both in an autosomal dominant and autosomal recessive manner and have been reported to cause a wide range of clinical phenotypes. TTN-associated conditions with cardiac manifestations include autosomal dominant dilated cardiomyopathy 1G (MIM: 604145), autosomal dominant familial hypertrophic cardiomyopathy 9 (MIM: 613765), and autosomal recessive Salih myopathy (MIM: 611705). Other genetic and/or environmental factors may influence the clinical phenotype. For recent information about properties and function of the titin protein see review authored by Linke and Hamdani (2014). References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. Linke WA and Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068. |
| Fulgent Genetics, |
RCV002499501 | SCV002781624 | 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 | 2021-10-22 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV001810601 | SCV003819047 | uncertain significance | not provided | 2019-06-26 | criteria provided, single submitter | clinical testing |