Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV003389298 | SCV004101334 | likely pathogenic | Dilated cardiomyopathy 1G | 2023-05-25 | criteria provided, single submitter | clinical testing | The TTN c.106928_106932del (p.Val35643AlafsTer5) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant is located in exon 360 of the meta transcript of titin and within the M-line, which is highly expressed in cardiac tissue (PMID: 25589632). In a meta-analysis of TTN truncating variants in DCM patients and controls, variants in this region were associated with a significantly increased risk of developing DCM (odds ratio 3.7) (PMID: 27869827). To our knowledge, this variant has not been reported in the peer-reviewed literature. It is also not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.106928_106932del (p.Val35643AlafsTer5) variant is classified as likely pathogenic for dilated cardiomyopathy. |