Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522907 | SCV000620469 | uncertain significance | not provided | 2017-09-01 | criteria provided, single submitter | clinical testing | The c.12492delA variant of uncertain significance in the TTN gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.12492delA variant causes a shift in reading frame starting at codon tyrosine 4165, changing it to a methionine, and creating a premature stop codon at position 4 of the new reading frame, denoted p.Tyr4165MetfsX4. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. However, other truncating TTN variants have been reported in approximately 3% of control alleles and the c.12492delA variant is not located in the A-band region of titin, where the majority of truncating pathogenic variants associated with DCM have been reported (Herman et al., 2012). |