Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Medicine Center of Excellence, |
RCV003989305 | SCV004808143 | uncertain significance | Dilated cardiomyopathy 1G | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV001507592 | SCV003826009 | uncertain significance | not provided | 2023-08-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001507592 | SCV001813200 | likely benign | not provided | 2019-11-04 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25979592, 24503780) |
| Mayo Clinic Laboratories, |
RCV001507592 | SCV001713223 | uncertain significance | not provided | 2020-07-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000618423 | SCV000735154 | uncertain significance | Cardiovascular phenotype | 2019-09-26 | criteria provided, single submitter | clinical testing | The p.G13318R variant (also known as c.39952G>A), located in coding exon 145 of the TTN gene, results from a G to A substitution at nucleotide position 39952. The glycine at codon 13318 is replaced by arginine, an amino acid with dissimilar properties. This variant was reported in one individual with dilated cardiomyopathy (DCM) and in another individual with hypertrophic cardiomyopathy (HCM), both of which also had variants in other cardiac-related genes (Pugh TJ et al. Genet Med. 2014;16(8):601-8 (reported as p.G19815R (c.59443G>A), Waldmüller et al. Mol Cell Probes. 2015 Oct;29(5):308-14 (reported as p.G20742R (c.62224G>A)). 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 variant remains unclear. |
| Labcorp Genetics |
RCV000462522 | SCV000542317 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 22383 of the TTN protein (p.Gly22383Arg). There is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs372388682, ExAC 0.02%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 47249). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Laboratory for Molecular Medicine, |
RCV000040519 | SCV000064210 | uncertain significance | not specified | 2012-01-19 | criteria provided, single submitter | clinical testing | The Gly19815Arg variant (TTN) has been identified in 1/6589 European American ch romosomes by the NHLBI Exome Sequencing Project in a broad population (http://ev s.gs.washington.edu/EVS). Computational analyses (biochemical amino acid propert ies, conservation, AlignGVGD and SIFT) do not provide strong support for or agai nst pathogenicity. Additional information is needed to fully assess the clinical significance of the Gly19815Arg variant. |