ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.81037C>T (p.Arg27013Ter) (rs869038795)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256162 SCV000322337 pathogenic not provided 2018-03-02 criteria provided, single submitter clinical testing The R25372X pathogenic variant in the TTN gene has been reported previously in association with DCM in two individuals from a French Canadian family (Chami et al., 2014). This variant has also been identified independently and/or in conjunction with additional cardiogenetic variants in individuals referred for cardiomyopathy genetic testing at GeneDx. So far, segregation data is limited or absent for this individual due to the lack of clinical information provided and/or insufficient participation by informative family members. The R25372X variant is predicted to cause loss of normal protein function either due to production of an abnormal, prematurely truncated protein, or by absence of protein product due to nonsense mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012). However, R25372X is 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). Furthermore, the R25372X variant is not observed in large population cohorts (Lek et al., 2016).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000256162 SCV000335307 likely pathogenic not provided 2015-09-11 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001256713 SCV001433116 pathogenic Dilated cardiomyopathy 1A 2019-12-18 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV001265557 SCV001443711 pathogenic Cardiomyopathy 2020-01-10 criteria provided, single submitter clinical testing This nonsense variant found in exon 326 of 363 is predicted to result in loss of normal protein function. This variant has been previously reported as a heterozygous change in patients with dilated cardiomyopathy (PMID: 25448463). ClinVar contains an entry for this variant (Variation ID: 265437). This variant occurs in the A-band of the protein where pathogenic truncating variants associated with dilated cardiomyopathy are enriched (PMID: 22335739). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Based on the available evidence, the c.81037C>T (p.Arg27013Ter) variant is classified as Pathogenic.

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