Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001802255 | SCV002050005 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2021-06-23 | criteria provided, single submitter | clinical testing | The GALT c.241G>C; p.Ala81Pro variant (rs111033665) is reported to be in compound heterozygous state with a pathogenic GALT variant p.Gln188Arg in the literature in an individual affected with mild galactosemia (Ohlsson 2019). This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 81 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.761). Additionally, another variant at this codon (c.241G>A; p.Ala81Thr) has been reported in individuals with galactosemia. Based on available information, the p.Ala81Pro variant is considered to be likely pathogenic. References: Ohlsson A et al. Heterogeneity of disease-causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants. J Inherit Metab Dis. 2019 Sep;42(5):1008-1018. PMID: 31194895. |
| Labcorp Genetics |
RCV001802255 | SCV002170503 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 81 of the GALT protein (p.Ala81Pro). This variant is present in population databases (rs111033665, gnomAD 0.002%). This missense change has been observed in individual(s) with galactose-1-phosphate uridylyltransferase deficiency (PMID: 31194895). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1330596). 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. 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: 1427861). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |