Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000184385 | SCV000237010 | uncertain significance | not provided | 2014-09-03 | criteria provided, single submitter | clinical testing | p.Leu12018Ter (TTA>TAA): c.36053 T>A in exon 175 of the TTN gene (NM_001256850.1) The L12018X variant in the TTN gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The L12018X variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, L12018X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. However, this variant is not located in the A-band region of titin, where the majority of mutations associated with DCM have been reported (Herman D et al., 2012). Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman D et al., 2012). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s). |