Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001060224 | SCV001224901 | uncertain significance | Hereditary motor and sensory neuropathy, Okinawa type; Hereditary spastic paraplegia 57 | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 222 of the TFG protein (p.Val222Ile). This variant is present in population databases (rs144368144, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TFG-related conditions. ClinVar contains an entry for this variant (Variation ID: 855052). 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 TFG 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. |
Ambry Genetics | RCV002365732 | SCV002666341 | uncertain significance | Inborn genetic diseases | 2019-09-20 | criteria provided, single submitter | clinical testing | The p.V222I variant (also known as c.664G>A), located in coding exon 5 of the TFG gene, results from a G to A substitution at nucleotide position 664. The valine at codon 222 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is 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. |
Gene |
RCV003442184 | SCV004168910 | uncertain significance | not provided | 2023-05-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |