Submissions for variant NM_001267550.2(TTN):c.76124A>T (p.Tyr25375Phe)

gnomAD frequency: 0.00001  dbSNP: rs374494927

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152212	SCV000200980	uncertain significance	not specified	2014-04-15	criteria provided, single submitter	clinical testing	The Tyr22807Phe variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/8264 European American chromoso mes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). C omputational prediction tools and conservation analysis suggest that this varian t may impact the protein, though this information is not predictive enough to de termine pathogenicity. Additional information is needed to fully assess the clin ical significance of the Tyr22807Phe variant.
Genetic Services Laboratory, University of Chicago	RCV000152212	SCV000597680	uncertain significance	not specified	2017-04-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727226	SCV000706753	uncertain significance	not provided	2017-03-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642829	SCV000764516	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-10	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001171265	SCV001333974	uncertain significance	Cardiomyopathy	2018-06-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000727226	SCV001811815	likely benign	not provided	2020-10-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336302	SCV002635701	uncertain significance	Cardiovascular phenotype	2020-03-06	criteria provided, single submitter	clinical testing	The p.Y16310F variant (also known as c.48929A>T), located in coding exon 153 of the TTN gene, results from an A to T substitution at nucleotide position 48929. The tyrosine at codon 16310 is replaced by phenylalanine, an amino acid with highly similar properties. 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.