Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000799905 | SCV000939591 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-12-31 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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). ClinVar contains an entry for this variant (Variation ID: 645756). This variant is also known as c.58845delA, c.50916delA, and p.K16972fs. This premature translational stop signal has been observed in individual(s) with centronuclear myopathy and/or dilated cardiomyopathy (PMID: 23975875, 32746448). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val19541Phefs*22) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. |
Gene |
RCV001561255 | SCV001783818 | likely pathogenic | not provided | 2023-05-15 | criteria provided, single submitter | clinical testing | Variant (reported as c.50916delA due to alternate nomenclature) has been reported in the literature in a patient with autosomal recessive centronuclear myopathy (CNM) who also harbored the E6077K variant in the TTN gene (Ceyhan-Birsoy et al., 2013); Frameshift 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 (Herman et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23975875, 22335739, 32746448, 32778822) |