Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001813757 | SCV000169430 | uncertain significance | not provided | 2022-08-04 | criteria provided, single submitter | clinical testing | Identified in unrelated patients with DCM, ARVC and unspecified skeletal myopathy in published literature (Campuzano et al. 2015; Forleo et al., 2017l Savarese et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.87711C>A p.(F29237) and c.68220 C>A p.(F22740L) due to use of alternate nomenclature/transcripts; This variant is associated with the following publications: (PMID: 34426522, 32039858, 24636144, 28750076, 26516846) |
Blueprint Genetics | RCV000208035 | SCV000264286 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2015-10-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000619452 | SCV000735687 | uncertain significance | Cardiovascular phenotype | 2020-03-25 | criteria provided, single submitter | clinical testing | The p.F22740L variant (also known as c.68220C>A), located in coding exon 170 of the TTN gene, results from a C to A substitution at nucleotide position 68220. The phenylalanine at codon 22740 is replaced by leucine, an amino acid with highly similar properties. This variant was detected in an individual with arrhythmogenic right ventricular cardiomyopathy who also had variants in the OBSCN gene (Forleo C et al. PLoS ONE, 2017 Jul;12:e0181842). This amino acid position is not well 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. |
Invitae | RCV000643873 | SCV000765560 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-12-19 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001170758 | SCV001333364 | uncertain significance | Cardiomyopathy | 2019-03-14 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000125950 | SCV001748737 | uncertain significance | not specified | 2022-07-19 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.87711C>A (p.Phe29237Leu) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 248118 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4e-05 vs 0.00039), allowing no conclusion about variant significance. c.87711C>A has been reported in the literature in individuals affected with Dilated Cardiomyopathy and ARVC (Campuzano_2015, Forleo_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Fulgent Genetics, |
RCV002498612 | SCV002781971 | 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 | 2022-04-07 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001813757 | SCV003824829 | uncertain significance | not provided | 2023-01-09 | criteria provided, single submitter | clinical testing |