Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Loeys Lab, |
RCV001375662 | SCV001572590 | pathogenic | Primary dilated cardiomyopathy | 2021-02-26 | criteria provided, single submitter | clinical testing | This sequence change results in a truncating variant of the TTN gene (p.(Val26839Leufs*5))The variant is absent in population databases such as gnomAD (PM2). The variant has not been described before. Functional studies have not been performed. However truncating and frameshift mutations in TTN are a well-known mechanism for dilated cardiomyopathy (PMID: 22335739) (PVS1). The variant is located in the A-band of the titin-protein which is a known hotspot for pathogenic variants (PM1). This variant was identified in 2 unrelated patients with DCM, and co-segregated in one family with DCM (for the second family no data on cosegregation was available) (PP1). In conclusion this variant was classified as pathogenic according to ACMG-guidelines (PVS1, PM1, PM2, PP1). |