Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000723449 | SCV000227033 | uncertain significance | not provided | 2015-09-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001851993 | SCV002262066 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 81 of the GALT protein (p.Ala81Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of galactosemia and/or galactose-1-phosphate uridylyltransferase deficiency (PMID: 1427861; Invitae). ClinVar contains an entry for this variant (Variation ID: 25141). 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 expected to disrupt GALT protein function with a positive predictive value of 80%. This variant disrupts the p.Ala81 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31194895). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |