ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.106954C>T (p.Arg35652Ter)

gnomAD frequency: 0.00001  dbSNP: rs565675340
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001228460 SCV001400860 pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-08-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg35652*) 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 present in population databases (rs565675340, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive TTN-related conditions and dilated cardiomyopathy (PMID: 25326637, 27625338, 36264615). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Arg33084*. ClinVar contains an entry for this variant (Variation ID: 242530). 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). Truncating variants in this region have also been identified in individuals affected with autosomal dominant dilated cardiomyopathy and/or cardio-related conditions (PMID: 27869827, 32964742, Invitae internal data). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001782733 SCV002021485 likely pathogenic not provided 2020-04-07 criteria provided, single submitter clinical testing
GeneDx RCV001782733 SCV005902977 pathogenic not provided 2024-09-30 criteria provided, single submitter clinical testing 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 M-line region of TTN in which the majority of loss of function variants have been associated with autosomal recessive titinopathies (PMID: 17444505); Reported in an individual with dilated cardiomyopathy (DCM) (PMID: 36264615); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17444505, 31691645, 36264615, 25326637, 38438525)

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