ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.78980G>A (p.Arg26327Gln)

gnomAD frequency: 0.00007  dbSNP: rs370367786
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040639 SCV000064330 uncertain significance not specified 2012-05-31 criteria provided, single submitter clinical testing The Arg23759Gln variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. However, this variant has been identified in 0.02% (1/6636) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computation al analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhe n2, and SIFT) do not provide strong support for or against an impact to the prot ein. In summary, additional information is needed to fully assess the clinical significance of the Arg23759Gln variant.
GeneDx RCV000040639 SCV000237585 uncertain significance not specified 2014-02-28 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 DCM-CRDM panel(s).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798181 SCV002042996 uncertain significance Cardiomyopathy 2019-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336153 SCV002641402 uncertain significance Cardiovascular phenotype 2018-05-30 criteria provided, single submitter clinical testing The p.R17262Q variant (also known as c.51785G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 51785. The arginine at codon 17262 is replaced by glutamine, an amino acid with highly similar properties. This alteration was reported (as NM_133378.4:c.71276G>A p.R23759Q) in one individual with dilated cardiomyopathy (DCM) who also had variants in other cardiac-related genes (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8). This amino acid position is highly 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 RCV002504913 SCV002816840 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 2021-09-30 criteria provided, single submitter clinical testing

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.