Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000735003 | SCV000196828 | uncertain significance | not provided | 2020-11-02 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Eurofins Ntd Llc |
RCV000735003 | SCV000863190 | uncertain significance | not provided | 2018-08-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001243305 | SCV001416453 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 9 of the FKTN protein (p.Val9Phe). This variant is present in population databases (rs145387221, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 162566). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FKTN protein function. 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. |
| ARUP Laboratories, |
RCV000735003 | SCV002506222 | uncertain significance | not provided | 2022-02-08 | criteria provided, single submitter | clinical testing | The FKTN c.25G>T; p.Val9Phe variant (rs145387221), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 162566). This variant is found in the African population with an allele frequency of 0.11% (28/24966 alleles) in the Genome Aggregation Database. The valine at codon nine is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.587). However, given the lack of clinical and functional data, the significance of the p.Val9Phe variant is uncertain at this time. |
| Ambry Genetics | RCV002426707 | SCV002743036 | uncertain significance | Cardiovascular phenotype | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.V9F variant (also known as c.25G>T), located in coding exon 1 of the FKTN gene, results from a G to T substitution at nucleotide position 25. The valine at codon 9 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly 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. |
| Fulgent Genetics, |
RCV002483297 | SCV002784766 | uncertain significance | Dilated cardiomyopathy 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Autosomal recessive limb-girdle muscular dystrophy type 2M; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 | 2021-10-14 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001243305 | SCV002078733 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2021-03-16 | no assertion criteria provided | clinical testing |