Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000003801 | SCV000479771 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2017-04-27 | criteria provided, single submitter | clinical testing | The GALT c.957C>A (p.His319Gln) variant has been reported in four patient studies in which it is identified in a total of six individuals with galactosemia, including one in a homozygous state, three in a compound heterozygous state, and two in a heterozygous state without a second identified variant (Reichardt et al., 1993; Maceratesi et al., 1996; Singh et al., 2012; Schadewaldt et al., 2014). The p.His319Gln variant was absent from 178 control alleles and is reported at a frequency of 0.00001 in the European (non-Finnish) population of the Exome Aggregation Consortium, but this is based on one allele only in an area of good coverage so the variant is presumed to be rare. In a study by Reichardt et al. (1993), expression analysis of the variant in COS7 cells showed undetectable enzyme activity. Further analysis of transfected cells carrying the p.His319Gln variant failed to detect appreciable amounts of protein whilst having a high level of mRNA, suggesting the p.His319Gln variant encodes an unstable polypeptide. The residue resides in a domain that is conserved in E.coli and yeast and is located in the metal binding site of GALT (McCorvie et al. 2016). Schadewalt et al. (2014) and Singh et al. (2012) also found low levels of GALT enzyme activity in patients with the p.His319Gln variant ranging from 18% to less than 1.5% of control levels. Based on the evidence, the p.His319Gln variant is classified as pathogenic for galactosemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV000003801 | SCV000821132 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 319 of the GALT protein (p.His319Gln). This variant is present in population databases (rs111033792, gnomAD 0.0009%). This missense change has been observed in individual(s) with galactose-1-phosphate uridylyltransferase deficiency (PMID: 8499924, 8956044, 22944367, 23022339, 25268296). ClinVar contains an entry for this variant (Variation ID: 3617). 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. Experimental studies have shown that this missense change affects GALT function (PMID: 8499924). For these reasons, this variant has been classified as Pathogenic. |
| Eurofins Ntd Llc |
RCV000727567 | SCV000854805 | pathogenic | not provided | 2017-12-13 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000727567 | SCV001246078 | pathogenic | not provided | 2018-08-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000003801 | SCV004198504 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-11-23 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000727567 | SCV004226600 | pathogenic | not provided | 2022-10-05 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2, PM3, PS3, PS4_moderate |
| OMIM | RCV000003801 | SCV000023966 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 1993-03-01 | no assertion criteria provided | literature only | |
| Counsyl | RCV000003801 | SCV000788876 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2016-12-21 | no assertion criteria provided | clinical testing |