Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Rady Children's Institute for Genomic Medicine, |
RCV004545868 | SCV004046441 | likely pathogenic | TTN-related disorder | criteria provided, single submitter | clinical testing | This frameshifting variant in exon 326 of 363 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. This variant occurs in the A-band of the titin protein, which is enriched for pathogenic truncating variants associated with dilated cardiomyopathy (PMID: 22335739; 31849696; 25589632). Loss-of-function variation in TTN is an established mechanism of disease (PMID: 22335739; 25589632). The c.82912_82915del (p.Glu27638ThrfsTer16) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.82912_82915del (p.Glu27638ThrfsTer16) variant is classified as Likely Pathogenic. |