Submissions for variant NM_001267550.2(TTN):c.64454G>A (p.Arg21485Gln)

gnomAD frequency: 0.00001  dbSNP: rs746903647

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184716	SCV000237416	uncertain significance	not specified	2014-11-07	criteria provided, single submitter	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 CARDIOMYOPATHY panel(s).
Ambry Genetics	RCV000619422	SCV000737121	uncertain significance	Cardiovascular phenotype	2016-09-10	criteria provided, single submitter	clinical testing	The p.R12420Q variant (also known as c.37259G>A), located in coding exon 136 of the TTN gene, results from a G to A substitution at nucleotide position 37259. The arginine at codon 12420 is replaced by glutamine, an amino acid with highly similar properties, and is located in the A-band region of the N2-B isoform of the titin protein. This variant was previously reported in the SNPDatabase as rs746903647. Based on data from ExAC, the A allele has an overall frequency less than 0.01% (1/104750). This amino acid position is well conserved in available 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.
Fulgent Genetics, Fulgent Genetics	RCV002492838	SCV002792047	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	2021-10-29	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486752	SCV004240059	likely benign	Cardiomyopathy	2022-07-15	criteria provided, single submitter	clinical testing