ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.97050dup (p.Glu32351fs) (rs794729365)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000184363 SCV000236988 pathogenic not provided 2020-09-03 criteria provided, single submitter clinical testing Previously identified in patients with DCM (Gigli et al., 2019; Ramchand et al., 2020); One patient tested at GeneDx with limb-girdle muscular dystrophy and no reported cardiomyopathy inherited this variant from a parent with cardiomyopathy and mild muscle weakness; segregation data from other families have demonstrated segregation with cardiomyopathy and reduced penetrance; Not observed in large population cohorts (Lek et al., 2016); Variant is located in the A-band of the titin protein, where the majority of pathogenic truncating variants have been reported.; 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; This variant is associated with the following publications: (PMID: 31931689, 31514951)
Invitae RCV000543494 SCV000642484 pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-08-30 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TTN gene (p.Glu32351Argfs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 31514951, Invitae). ClinVar contains an entry for this variant (Variation ID: 202495). 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000184363 SCV000855473 likely pathogenic not provided 2017-07-12 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV001249379 SCV001423373 not provided Primary dilated cardiomyopathy no assertion provided phenotyping only Variant interpretted as Likely pathogenic and reported on 02-08-2015 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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