ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.87355del (p.Ala29119fs)

dbSNP: rs794729356
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000184349 SCV000236974 pathogenic not provided 2022-12-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation and nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (Herman et al., 2012); This variant is associated with the following publications: (PMID: 22335739, 28045975, 29253866)
Invitae RCV001852393 SCV002228986 pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-05-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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: 202484). This premature translational stop signal has been observed in individuals with dilated cardiomyopathy (PMID: 28045975, 29253866). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala29119Leufs*17) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.
Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen RCV000490908 SCV000298121 likely pathogenic Dilated cardiomyopathy 1S 2016-05-01 no assertion criteria provided clinical testing

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