Submissions for variant NM_001267550.2(TTN):c.101281C>T (p.Arg33761Trp)

gnomAD frequency: 0.00019  dbSNP: rs201421156

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154877	SCV000204559	uncertain significance	not specified	2015-01-20	criteria provided, single submitter	clinical testing	The p.Arg31193Trp variant in TTN has been previously identified by our laborator y in 1 adult with DCM. This variant has also been identified in 14/67674 Europea n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs201421156). Computational prediction tools and conservation ana lysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg31193Trp variant is uncertain.
Invitae	RCV000557649	SCV000642505	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-04-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621205	SCV000737225	uncertain significance	Cardiovascular phenotype	2019-11-19	criteria provided, single submitter	clinical testing	The p.R24696W variant (also known as c.74086C>T), located in coding exon 185 of the TTN gene, results from a C to T substitution at nucleotide position 74086. The arginine at codon 24696 is replaced by tryptophan, an amino acid with dissimilar properties, and is located in the M-band region of the N2-B isoform of the titin protein. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Eurofins Ntd Llc (ga)	RCV000185080	SCV000855216	uncertain significance	not provided	2017-09-19	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000185080	SCV002541909	uncertain significance	not provided	2021-08-20	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498745	SCV002814900	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	2021-09-08	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000185080	SCV003818365	uncertain significance	not provided	2020-06-30	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486693	SCV004240219	likely benign	Cardiomyopathy	2023-05-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000185080	SCV000237892	not provided	not provided	2014-04-29	no assertion provided	clinical testing	Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM-CRDM panel(s).
Clinical Genetics, Academic Medical Center	RCV000185080	SCV001919295	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000185080	SCV001968650	uncertain significance	not provided		no assertion criteria provided	clinical testing