Submissions for variant NM_001267550.2(TTN):c.6668A>T (p.His2223Leu)

gnomAD frequency: 0.00003  dbSNP: rs372979075

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172467	SCV000051339	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000172467	SCV000238023	likely benign	not provided	2020-07-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31983221)
Ambry Genetics	RCV000618905	SCV000736889	uncertain significance	Cardiovascular phenotype	2017-07-19	criteria provided, single submitter	clinical testing	The p.H2177L variant (also known as c.6530A>T), located in coding exon 27 of the TTN gene, results from an A to T substitution at nucleotide position 6530. The histidine at codon 2177 is replaced by leucine, an amino acid with similar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46 (reported as p.H2223L, c.6668A>T)). This amino acid position is highly conserved in available vertebrate species; however, leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642957	SCV000764644	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765589	SCV000896904	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2018-10-31	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852932	SCV000995676	likely benign	Hypertrophic cardiomyopathy	2017-07-06	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000172467	SCV003819680	uncertain significance	not provided	2021-04-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150043	SCV003838058	benign	Cardiomyopathy	2022-05-06	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000172467	SCV001924954	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000172467	SCV001970209	uncertain significance	not provided		no assertion criteria provided	clinical testing