Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040503 | SCV000064194 | uncertain significance | not specified | 2012-12-11 | criteria provided, single submitter | clinical testing | The Arg19461His variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has been identified in 1/8218 E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs72646868). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein . Additional information is needed to fully assess the clinical significance of the Arg19461His variant. |
Gene |
RCV000714070 | SCV000237438 | likely benign | not provided | 2018-11-08 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 28771489, 26567375) |
Eurofins Ntd Llc |
RCV000714070 | SCV000335246 | uncertain significance | not provided | 2015-09-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000460102 | SCV000542454 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2016-11-26 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000714070 | SCV000844737 | uncertain significance | not provided | 2017-12-06 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000714070 | SCV001474637 | uncertain significance | not provided | 2019-11-14 | criteria provided, single submitter | clinical testing | The TTN c.66086G>A; p.Arg22029His variant (rs72646868; ClinVar Variation ID: 47233) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Arg22029His variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. |
Ambry Genetics | RCV002362633 | SCV002623904 | uncertain significance | Cardiovascular phenotype | 2019-09-26 | criteria provided, single submitter | clinical testing | The p.R12964H variant (also known as c.38891G>A), located in coding exon 141 of the TTN gene, results from a G to A substitution at nucleotide position 38891. The arginine at codon 12964 is replaced by histidine, 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. |
Revvity Omics, |
RCV000714070 | SCV003822811 | uncertain significance | not provided | 2022-09-13 | criteria provided, single submitter | clinical testing |