ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.34570C>T (p.Arg11524Ter)

gnomAD frequency: 0.00001  dbSNP: rs1441434215
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000642807 SCV000764494 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-02-06 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, 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: 535046). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg11524*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170391 SCV001332968 uncertain significance Cardiomyopathy 2018-10-19 criteria provided, single submitter clinical testing
GeneDx RCV002285385 SCV002575323 uncertain significance not provided 2022-03-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; Not located in a region of TTN in which loss of function variants are significantly associated with titinopathies
Fulgent Genetics, Fulgent Genetics RCV002477416 SCV002786103 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 2021-09-04 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV004545796 SCV003807780 likely pathogenic TTN-related disorder 2022-04-01 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PM2 moderated

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