Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805776 | SCV000945744 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2022-12-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 650599). This missense change has been observed in individual(s) with galactosemia (PMID: 22743281; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 206 of the GALT protein (p.Gln206Arg). |
| ARUP Laboratories, |
RCV000805776 | SCV001157990 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2018-11-06 | criteria provided, single submitter | clinical testing | The GALT c.617A>G; p.Gln206Arg variant is reported in the literature in the homozygous state in an individual with classic galactosemia (Liu 2012). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glutamine at codon 206 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Consistent with these predictions, an in vitro GALT assay suggested the p.Gln206Arg variant exhibits negligible activity compared to wildtype protein (Spencer 2013). Based on available information, this variant is considered to be likely pathogenic. References: Liu Y et al. N- and O-linked glycosylation of total plasma glycoproteins in galactosemia. Mol Genet Metab. 2012 Aug;106(4):442-54. Spencer JB et al. Modifiers of ovarian function in girls and women with classic galactosemia. J Clin Endocrinol Metab. 2013 Jul;98(7):E1257-65. |