Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000650360 | SCV000772203 | likely pathogenic | Congenital myasthenic syndrome 12 | 2023-02-11 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 70 of the GFPT1 protein (p.Asp70Gly). This variant is present in population databases (rs530830788, gnomAD 0.009%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: 540352). This missense change has been observed in individual(s) with GFPT1-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. |
Ambry Genetics | RCV003372790 | SCV004063249 | uncertain significance | Inborn genetic diseases | 2023-08-29 | criteria provided, single submitter | clinical testing | The c.209A>G (p.D70G) alteration is located in exon 3 (coding exon 3) of the GFPT1 gene. This alteration results from a A to G substitution at nucleotide position 209, causing the aspartic acid (D) at amino acid position 70 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |