Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001267515 | SCV001445696 | uncertain significance | Inborn genetic diseases | 2020-09-09 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change:_x000D_ _x000D_ The c.1255T>C (p.F419L) alteration is located in coding exon 13 of the GFPT1 gene. This alteration results from a T to C substitution at nucleotide position 1255, causing the phenylalanine (F) at amino acid position 419 to be replaced by a leucine (L). The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the GFPT1 c.1255T>C alteration was not observed, with coverage at this position. The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.F419 amino acid is conserved in available vertebrate species. The alteration is predicted inconclusive by in silico modeling:_x000D_ _x000D_ The in silico prediction for the p.F419L alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001880148 | SCV002306516 | uncertain significance | Congenital myasthenic syndrome 12 | 2023-04-04 | criteria provided, single submitter | clinical testing | 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. 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 GFPT1 protein function. ClinVar contains an entry for this variant (Variation ID: 986215). This variant has not been reported in the literature in individuals affected with GFPT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 437 of the GFPT1 protein (p.Phe437Leu). |
| Muscle and Diseases Team, |
RCV004587096 | SCV005038557 | pathogenic | GFPT1-related myopathy with protein aggregates and rimmed vacuoles | 2024-03-01 | criteria provided, single submitter | research | PVS1+PS3+PM2+PP3+PP4+PP5 |