Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000634557 | SCV000755886 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 223 of the GALT protein (p.Arg223Cys). This variant is present in population databases (rs111033750, gnomAD 0.008%). This missense change has been observed in individual(s) with galactose-1-phosphate uridylyltransferase deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 529225). 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.Arg223 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17876724, 22461411). 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. |
Eurofins Ntd Llc |
RCV000733886 | SCV000861989 | uncertain significance | not provided | 2018-06-19 | criteria provided, single submitter | clinical testing | |
Medical Cytogenetics and Molecular Genetics Laboratory, |
RCV001270213 | SCV001364344 | pathogenic | Premature ovarian failure | 2020-03-02 | criteria provided, single submitter | research | |
Natera, |
RCV001835014 | SCV002085228 | uncertain significance | Galactosemia | 2019-01-03 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003892439 | SCV004709341 | uncertain significance | GALT-related disorder | 2024-02-03 | no assertion criteria provided | clinical testing | The GALT c.667C>T variant is predicted to result in the amino acid substitution p.Arg223Cys. This variant was reported in the heterozygous state without a second GALT variant in an individual with primary ovarian insufficiency (described as c.C304T, p.R114C in Bestetti et al. 2021. PubMed ID: 34480478). We have observed this variant along with the Duarte variant in an individual with an abnormal newborn screen for galactosemia (PreventionGenetics internal data). Additionally, a different substitution of the same amino acid (p.Arg223Ser) was reported along with a known pathogenic GALT variant in a study of individuals with abnormal newborn screening results for galactosemia (Calderon et al. 2007. PubMed ID: 17876724). This variant is reported in 0.012% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-34648433-C-T). Although we suspect this variant may be pathogenic, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. |