Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |
Gene |
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, |
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, |
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 |