Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Laboratory, |
RCV003988186 | SCV004803180 | likely pathogenic | Dilated cardiomyopathy 1G | 2021-06-04 | criteria provided, single submitter | clinical testing | • The p.Glu26126Alafs*3 variant in the TTN gene has not been previously reported in association with disease. • This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). • This variant results in a 8bp insertion, which causes a shift in the protein reading frame, leading to a premature termination codon 3 amino acids downstream. Heterozygous loss of function is an established mechanism of disease for the TTN gene. • The p.Glu26126Alafs*3 variant is located in the A-band of the titin protein. Other pathogenic and likely pathogenic truncating variants have been described in the A-band. • These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Glu26126Alafs*3 variant as likely pathogenic for dilated cardiomyopathy in an autosomal dominant manner based on the information above. [ACMG evidence codes used: PVS1_strong; PM2] |