Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000184356 | SCV000236981 | likely pathogenic | not provided | 2013-01-09 | criteria provided, single submitter | clinical testing | c.85730_85731delCA: p.Thr28577SerfsX17 (T28577SfsX17) in exon 285 of the TTN gene (NM_001256850.1). The normal sequence with the bases that are deleted in braces is: ATTA{CA}GTCA. The c.85730_85731delCA variant in the TTN gene has not been reported previously as pathogenic nor as a benign polymorphism to our knowledge. This small deletion causes a shift in reading frame starting at codon Threonine 28577, changing it to a Serine, and creating a premature stop codon at position 17 of the new reading frame, denoted p.Thr28577SerfsX17. c.85730_85731delCA is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. This likely pathogenic variant is 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). In summary, c.85730_85731delCAin the TTN gene is a likely pathogenic variant. |
Invitae | RCV003765153 | SCV004606641 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr30218Serfs*17) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 202491). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |