Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001363357 | SCV001559466 | uncertain significance | Hereditary motor and sensory neuropathy, Okinawa type; Hereditary spastic paraplegia 57 | 2020-03-05 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with TFG-related conditions. This sequence change replaces isoleucine with valine at codon 12 of the TFG protein (p.Ile12Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002341769 | SCV002618678 | uncertain significance | Inborn genetic diseases | 2020-01-30 | criteria provided, single submitter | clinical testing | The p.I12V variant (also known as c.34A>G), located in coding exon 1 of the TFG gene, results from an A to G substitution at nucleotide position 34. The isoleucine at codon 12 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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. |