Submissions for variant NM_001267550.2(TTN):c.11311+1910C>G

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV004529674	SCV004106501	uncertain significance	TTN-related disorder	2023-05-01	criteria provided, single submitter	clinical testing	The TTN c.11186C>G variant is predicted to result in premature protein termination (p.Ser3729*). This variant has been reported as a modifier of hypertrophic cardiomyopathy (reported as c.C11186G in Table S2 - Zhang et al. 2017. PubMed ID: 28822653). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is located in exon 46 of the Novex-3 transcript (minor small cardiac isoform) which is the last exon of this transcript. This exon is not included in any other TTN transcripts (principle cardiac or skeletal muscle isoforms) and would be referred to as c.11311+1910C>G with NM_001267550.2. Several TTN truncating variants in this exon have been reported in presumably healthy control individuals and to our knowledge no loss of function variants in this exon have been reported in congenital titinopathy cases (Roberts et al. 2015. PMID: 25589632; https://www.cardiodb.org/titin/titin_exon.php?id=48). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.