Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000806470 | SCV000946473 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2023-07-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GALC function (PMID: 10234611, 27126738, 27638593). 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 GALC protein function. ClinVar contains an entry for this variant (Variation ID: 651170). This missense change has been observed in individual(s) with infantile Krabbe disease (PMID: 10234611, 22115770). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs757407613, gnomAD 0.003%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 335 of the GALC protein (p.Tyr335Cys). |
Gene |
RCV002279541 | SCV002567620 | pathogenic | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect (significantly reduced GALC activity) (Fu et al., 1999); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10234611, 27638593, 27126738, 22115770) |
Natera, |
RCV000806470 | SCV002093639 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2020-08-27 | no assertion criteria provided | clinical testing |