Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000184322 | SCV000236947 | likely pathogenic | not provided | 2012-11-18 | criteria provided, single submitter | clinical testing | c.64722delT: p.Ser21574ArgfsX19 (S21574RfsX19) in exon 275 of the TTN gene (NM_001256850.1). The normal sequence with the base that is deleted in braces is: TCAG{T}GCAG. The c.64722delT variant in the TTN gene has not been reported previously as pathogenic nor as a benign polymorphism, to our knowledge. c.64722delT causes a shift in reading frame starting at codon Serine 21574, changing it to an Arginine, and creating a premature stop codon at position 19 of the new reading frame, denoted p.Ser21574ArgfsX19. 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. c.64722delT 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, while the c.64722delT variant in the TTN gene is likely a pathogenic variant, the possibility it is a rare benign variant cannot be excluded. |