Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040217 | SCV000063908 | likely pathogenic | Primary dilated cardiomyopathy | 2011-11-16 | criteria provided, single submitter | clinical testing | The Val11303fs variant (TTN) has not been previous reported but has been identif ied by our laboratory in 1 individual with DCM. This variant is predicted to cau se a frameshift, which alters the protein's amino acid sequence beginning at cod on 11303 and leads to a premature stop codon 7 amino acids downstream. This alte ration is then predicted to lead to a truncated or absent protein (loss of funct ion). Loss of function variants in TTN are common in patients with DCM (Jon Seid man, pers. comm.). In summary, this variant is likely to be pathogenic. |
Gene |
RCV000184297 | SCV000236922 | uncertain significance | not provided | 2013-05-20 | criteria provided, single submitter | clinical testing | c.36687delA: p.Val12230SerfsX7 (V12230SfsX7) in exon 177 of the TTN gene (NM_001256850.1). The normal sequence with the base that is deleted in braces is: tagA{A}GTCA, with intronic sequence in lowercase letters and exonic sequence in uppercase letters. The c.36687delA variant in the TTN gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. This variant causes a shift in reading frame starting at codon Valine 12230, changing it to a Serine, and creating a premature stop codon at position 7 of the new reading frame, denoted p.Val12230SerfsX7. 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, truncating TTN variants have been reported in approximately 3% of control alleles (Herman D et al., 2012), and c.36687delA is not located in the A-band region of titin, where the majority of truncating mutations associated with DCM have been reported (Herman D et al., 2012). With the clinical and molecular information available at this time, we cannot definitively determine if c.36687delA is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). |