Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000396885 | SCV000336065 | uncertain significance | not provided | 2018-08-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000687793 | SCV000815380 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 146 of the FKTN protein (p.Arg146Gln). This variant is present in population databases (rs143748939, gnomAD 0.04%). 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: 283759). 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 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. |
Gene |
RCV000396885 | SCV001752381 | uncertain significance | not provided | 2021-05-19 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Genetic Services Laboratory, |
RCV001820816 | SCV002071527 | uncertain significance | not specified | 2020-07-17 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the FKTN gene demonstrated a sequence change, c.437G>A, in exon 6 that results in an amino acid change, p.Arg146Gln. This sequence change does not appear to have been previously described in patients with FKTN-related disorders and has been described in the gnomAD database with a low frequency of 0.04% in the Finnish sub-population (dbSNP rs143748939). The p.Arg146Gln change affects a highly conserved amino acid residue located in a domain of the FKTN protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg146Gln substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg146Gln change remains unknown at this time. |
Ambry Genetics | RCV002328768 | SCV002633012 | uncertain significance | Cardiovascular phenotype | 2021-12-23 | criteria provided, single submitter | clinical testing | The p.R146Q variant (also known as c.437G>A), located in coding exon 4 of the FKTN gene, results from a G to A substitution at nucleotide position 437. The arginine at codon 146 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002502111 | SCV002812314 | 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 | 2021-08-03 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000396885 | SCV003832688 | uncertain significance | not provided | 2020-09-24 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000687793 | SCV002079570 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2020-01-24 | no assertion criteria provided | clinical testing |