ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.104413C>T (p.Arg34805Ter)

gnomAD frequency: 0.00001  dbSNP: rs750519430
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000337217 SCV000345318 likely pathogenic not provided 2016-09-05 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000337217 SCV001371165 pathogenic not provided 2020-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001377610 SCV001574990 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-12-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg34805*) 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 (rs750519430, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with centronuclear myopathy, dilated cardiomyopathy and clinical features of TTN-related conditions (PMID: 31737537, 33820833, 34958143, 36264615). ClinVar contains an entry for this variant (Variation ID: 290707). 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). 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.
Revvity Omics, Revvity RCV000337217 SCV002021499 likely pathogenic not provided 2020-04-02 criteria provided, single submitter clinical testing
GeneDx RCV000337217 SCV005326634 likely pathogenic not provided 2024-03-14 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); Observed in an individual with dilated cardiomyopathy; however, it is unclear whether the variant was observed independently or in conjunction with another TTN variant (PMID: 31737537); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34958143, 33820833, 17444505, 31737537)

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