Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000039871 | SCV000063562 | likely pathogenic | Neuromuscular disease | 2013-09-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001245126 | SCV001418395 | pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-03-18 | criteria provided, single submitter | clinical testing | This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 46601). This variant is also known as c.11764+1G>A. Disruption of this splice site has been observed in individuals with autosomal recessive centronuclear myopathy (PMID: 23975875, 29691892, 31053406). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 52 of the TTN gene. It is expected to disrupt RNA splicing and likely results in a truncated or disrupted TTN protein. |