Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Klaassen Lab, |
RCV000853166 | SCV000995880 | likely pathogenic | Familial restrictive cardiomyopathy | 2019-07-03 | criteria provided, single submitter | research | |
Revvity Omics, |
RCV001784466 | SCV002021492 | uncertain significance | not provided | 2022-03-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001858516 | SCV002171528 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 321 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs536078303, gnomAD 0.08%). This variant has been observed in individual(s) with restrictive cardiomyopathy (PMID: 31568572). ClinVar contains an entry for this variant (Variation ID: 691834). 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. |