Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040456 | SCV000064147 | uncertain significance | not specified | 2012-04-04 | criteria provided, single submitter | clinical testing | The Arg18359His variant (TTN) has not been previously reported in the literature , but has been identified in 1 individual with DCM tested by our laboratory. Com putational analyses (biochemical amino acid properties, conservation, AlignGVGD and PolyPhen2) do not provide strong support for or against an impact to the pro tein. Additional information is needed to fully assess the clinical significance of the Arg18358His variant. |
| Gene |
RCV000767112 | SCV000621303 | uncertain significance | not provided | 2017-09-28 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TTN gene. The R19286H variant (reported as R18359H due to the use of alternate nomenclature) has been reported as a variant of uncertain significance in one patient with DCM (Pugh et al., 2014); however, additional clinical and segregation information were not provided. The R19286H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this is a missense variant in a gene in which most reported pathogenic variants associated with cardiomyopathy are truncating/loss-of-function (Stenson et al., 2014). Nevertheless, the R19286H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Finally, this substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. |
| Ambry Genetics | RCV002453328 | SCV002616614 | uncertain significance | Cardiovascular phenotype | 2018-07-09 | criteria provided, single submitter | clinical testing | The p.R11862H variant (also known as c.35585G>A), located in coding exon 131 of the TTN gene, results from a G to A substitution at nucleotide position 35585. The arginine at codon 11862 is replaced by histidine, an amino acid with highly similar properties. This alteration was reported as NM_133378.4:c.55076G>A p.R18359H in an individual with dilated cardiomyopathy (DCM); however, clinical details were limited (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, |
RCV002483016 | SCV002794506 | 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 | 2021-09-14 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000767112 | SCV003821126 | uncertain significance | not provided | 2019-06-27 | criteria provided, single submitter | clinical testing |