Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001056316 | SCV001220754 | uncertain significance | Hereditary motor and sensory neuropathy, Okinawa type; Hereditary spastic paraplegia 57 | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 385 of the TFG protein (p.Arg385His). This variant is present in population databases (rs373719892, gnomAD 0.01%). 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: 851831). 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. |
| ARUP Laboratories, |
RCV003117730 | SCV003799897 | uncertain significance | not provided | 2022-04-01 | criteria provided, single submitter | clinical testing | The TFG c.1154G>A; p.Arg385His variant (rs373719892), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 851831). This variant is found in the general population with an overall allele frequency of 0.004% (10/282038 alleles) in the Genome Aggregation Database. The arginine at codon 385 is highly conserved but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.323). Due to limited information, the clinical significance of this variant is uncertain at this time. |