Submissions for variant NM_001267550.2(TTN):c.38424del (p.Lys12809fs)

dbSNP: rs1553775991

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000642777	SCV000764464	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2019-07-18	criteria provided, single submitter	clinical testing	This sequence change results in a premature translational stop signal in the TTN gene (p.Lys12809Argfs*138). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the TTN protein. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with TTN-related disease. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262893	SCV001440929	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2019-01-01	criteria provided, single submitter	clinical testing