Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000486995 | SCV000333484 | likely pathogenic | not provided | 2015-07-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000486995 | SCV000570616 | pathogenic | not provided | 2023-07-25 | criteria provided, single submitter | clinical testing | Identified in a patient with peripartum cardiomyopathy in the published literature (PMID: 33874732); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (PMID: 22335739); This variant is associated with the following publications: (PMID: 22335739, 33874732) |
Invitae | RCV001227214 | SCV001399562 | pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln27346*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with dilated cardiomyopathy and/or peripartum cardiomyopathy (PMID: 33874732; Invitae). ClinVar contains an entry for this variant (Variation ID: 282174). 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. |