Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825047 | SCV000966246 | uncertain significance | not specified | 2018-06-04 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly15293S er variant in TTN has not been previously reported in individuals with cardiomyo pathy and was absent from large population studies. This variant is located in t he last base of exon 279, which is part of the 5? splice region. Computational t ools predict altered splicing which could lead to a loss of function of the TTN protein. However, this information is not predictive enough to determine pathoge nicity without RNA splicing studies. In summary, while there is some suspicion f or a pathogenic role, the clinical significance of the p.Gly15293Ser variant is uncertain. ACMG/AMP criteria applied: PM2, PP3. |
| Invitae | RCV003768548 | SCV004573148 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 17861 of the TTN protein (p.Gly17861Ser). This variant also falls at the last nucleotide of exon 278, which is part of the consensus splice site for this exon. 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: 666610). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is located in the A band of TTN (PMID: 25589632). Variants in this region may be relevant for cardiac or neuromuscular disorders (PMID: 25589632, 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |