ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.67660G>C (p.Gly22554Arg)

dbSNP: rs769525101
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000242079 SCV000318445 uncertain significance Cardiovascular phenotype 2013-01-31 criteria provided, single submitter clinical testing The p.G19986R variant (also known as c.59956G>C) is located in exon 269 (coding exon 268) of the TTN gene. This alteration results from a G to C substitution at nucleotide position 59956. The glycine at codon 19986 is replaced by arginine, an amino acid with dissimilar properties. This variant did not segregate with dilated cardiomyopathy in one family tested by our laboratory. This variant was observed in the proband and his affected nephew, and it was absent in the proband's affected brother. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be benign by PolyPhen in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.G19986R remains unclear.
GeneDx RCV000184751 SCV000237458 not provided not provided 2014-05-20 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.