ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.101107C>T (p.Arg33703Ter) (rs766265889)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Petrovsky Russian Research Center of Surgery, The Federal Agency for Scientific Organizations RCV000766232 SCV000891776 likely pathogenic Dilated cardiomyopathy 1G 2019-03-22 criteria provided, single submitter research We observed NM_001267550.2:c.101107C>T (p.Arg33703*) variant in male proband and proband's mother, both diagnosed with DCM. The c.101107C>T (p.Arg33703*) variant is, to our knowledge, very rare (MAF- 0.00001797 in the gnomAD). It is also a truncating variant located in constitutively expressed exon (PVS1 interpretation criteria). Based on this evidence and on family segregation data, we classify c.101107C>T (p.Arg33703*) variant as likely pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769860 SCV000901286 likely pathogenic Cardiomyopathy 2017-01-05 criteria provided, single submitter clinical testing
Invitae RCV000821045 SCV000961786 likely pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-08-14 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TTN gene (p.Arg33703*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is present in population databases (rs766265889, ExAC 0.001%). This variant has not been reported in the literature in individuals with TTN-related disease. This variant is located in the M band of TTN (PMID: 25589632). Truncating variants in this region have been previously reported in individuals affected with autosomal recessive myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473), but have not been definitively shown to cause cardiomyopathy (PMID: 25589632). 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.

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