ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.63010G>T (p.Glu21004Ter)

dbSNP: rs769345390
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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 RCV001205862 SCV001377141 pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-08-24 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). ClinVar contains an entry for this variant (Variation ID: 936945). This premature translational stop signal has been observed in individuals with dilated cardiomyopathy (PMID: 32998006; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu21004*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001568893 SCV001792845 pathogenic not provided 2019-03-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); 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 A-band region of titin, where the majority of truncating pathogenic variants associated with DCM have been reported (Herman et al., 2012).
GenomeConnect, ClinGen RCV001249243 SCV001423180 not provided Dilated cardiomyopathy 1G no assertion provided phenotyping only Variant interpretted as Pathogenic and reported on 04-02-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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