Submissions for variant NM_001267550.2(TTN):c.46843dup (p.Thr15615fs)

dbSNP: rs1553712292

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000540984	SCV000643226	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-08-28	criteria provided, single submitter	clinical testing	In summary, this truncating variant is found in the I-band of the TTN protein, where truncating variants have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739, 25589632). However, truncating variants in the I-band have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). For these reasons it has been classified as Likely Pathogenic. This variant identified in the TTN gene is located in the I band of the resulting protein (PMID: 25589632). This variant has been reported to be de novo in an individual affected with a TTN-related disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change inserts 1 nucleotide in exon 251 of the TTN mRNA (c.46843dupA), causing a frameshift at codon 15615. This creates a premature translational stop signal (p.Thr15615Asnfs*4) and is expected to result in a disrupted protein product.