ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.68286_68289dup (p.Trp22764fs)

dbSNP: rs2154174801
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001958583 SCV002232736 pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2022-02-10 criteria provided, single submitter clinical testing 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). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of dilated cardiomyopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp22764Asnfs*4) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.
GeneDx RCV002225953 SCV002504338 pathogenic not provided 2022-04-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); 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 titin, where the majority of truncating pathogenic variants associated with DCM have been reported (Herman et al., 2012); Reported in ClinVar as a pathogenic variant (ClinVar Variant ID# 1455326); reported by another clinical laboratory in individual(s) with clinical features of dilated cardiomyopathy, including at least one individual in which the variant was observed to be de novo (Clinvar Accession ID# SCV002232736.1); This variant is associated with the following publications: (PMID: 22335739)

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