Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696084 | SCV000824631 | pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 302 of the TTN gene. It is expected to disrupt RNA splicing and likely results in a truncated or disrupted TTN protein. This variant is present in population databases (rs553526525, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with dilated cardiomyopathy (PMID: 22335739, 29057560). It has also been observed to segregate with disease in related individuals. This variant is also known as c.55003+1G>A. ClinVar contains an entry for this variant (Variation ID: 574210). 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). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). 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. |
Gene |
RCV001528301 | SCV002496222 | pathogenic | not provided | 2023-09-19 | criteria provided, single submitter | clinical testing | Variant reported heterozygous in multiple unrelated patients with dilated cardiomyopathy (Herman et al., 2012; van den Hoogenhof et al., 2018; Marschall et al., 2019; Nguyen et al., 2021); Not observed at a significant frequency in large population cohorts (gnomAD); Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (Herman et al., 2012); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 29650543, 23975875, 29057560, 30847666, 32880476, 37183561, 36344503, 31112426, 32964742, 31737537, 22335739, 34011823, 33662488) |
Ce |
RCV001528301 | SCV004011264 | pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | TTN: PVS1:Strong, PM1, PM2, PS4:Moderate |
CHEO Genetics Diagnostic Laboratory, |
RCV003486921 | SCV004240060 | pathogenic | Cardiomyopathy | 2022-09-01 | criteria provided, single submitter | clinical testing | |
KTest Genetics, |
RCV001594401 | SCV001499991 | pathogenic | Dilated cardiomyopathy 1G | no assertion criteria provided | clinical testing | ||
Diagnostic Laboratory, |
RCV001528301 | SCV001739819 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001528301 | SCV001930986 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001528301 | SCV001959765 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV001528301 | SCV001978888 | pathogenic | not provided | no assertion criteria provided | clinical testing |