Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000319760 | SCV000332866 | uncertain significance | not provided | 2015-07-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000464716 | SCV000542323 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-26 | criteria provided, single submitter | clinical testing | This sequence change inserts 4 nucleotides in exon 362 of the TTN mRNA (c.107460_107463dupAGTC), causing a frameshift at codon 35822. This creates a premature translational stop signal (p.Gln35822Serfs*21) and is expected to result in an absent or disrupted protein product. This variant is found in the M-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the M-band of TTN previously reported in patients affected with various forms of myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473). For these reasons, this variant has been classified as Likely Pathogenic. |
Invitae | RCV001378679 | SCV001576302 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-07-12 | criteria provided, single submitter | clinical testing | 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. This variant is located in the M band of TTN (PMID: 25589632). Truncating variants in this region have been previously reported in individuals affected with autosomal recessive myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473), but have not been definitively shown to cause cardiomyopathy (PMID: 25589632). ClinVar contains an entry for this variant (Variation ID: 404666). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln35822Serfs*21) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. |