Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000184367 | SCV000236992 | uncertain significance | not provided | 2014-08-28 | criteria provided, single submitter | clinical testing | c.97227delT: p.Asp32410ThrfsX4 (D32410TfsX4) in exon 308 of the TTN gene (NM_001256850.1). The normal sequence with the bases that are deleted in braces is: (TTGT[T]GACC). Truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM (Herman D et al., 2012). However, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles (Herman D et al., 2012). TTN mutations may also be associated with congenital cardiac and skeletal myopathies, hereditary myopathy with early respiratory failure, tibial muscular dystrophy, and limb-girdle muscular dystrophy (Lange S et al., 2005; Hackman P et al., 2002; Carmignac V et al., 2007; Hackman P et al., 2008). Although the c.97227delT variant in the TTN gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Aspartic acid 32410, changing it to a Threonine, and creating a premature stop codon at position 4 of the new reading frame, denoted p.Asp32410ThrfsX4. 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, this variant is not located in the A-band region of the titin, where the majority of truncating mutations associated with DCM have been reported (Herman D et al., 2012). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s). |