Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000490237 | SCV000576926 | uncertain significance | not provided | 2018-09-13 | criteria provided, single submitter | clinical testing | The I119M variant in the FKBP14 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I119M variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I119M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I119M as a variant of uncertain significance. |
Invitae | RCV000698654 | SCV000827334 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic and deafness type | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 119 of the FKBP14 protein (p.Ile119Met). This variant is present in population databases (rs202182643, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with FKBP14-related conditions. ClinVar contains an entry for this variant (Variation ID: 426476). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Knight Diagnostic Laboratories, |
RCV001270094 | SCV001448911 | uncertain significance | Hypotonia | 2019-05-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002455946 | SCV002613596 | uncertain significance | Cardiovascular phenotype | 2021-11-09 | criteria provided, single submitter | clinical testing | The p.I119M variant (also known as c.357T>G), located in coding exon 3 of the FKBP14 gene, results from a T to G substitution at nucleotide position 357. The isoleucine at codon 119 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
Mayo Clinic Laboratories, |
RCV000490237 | SCV004224004 | uncertain significance | not provided | 2022-10-11 | criteria provided, single submitter | clinical testing |