Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000415223 | SCV000492714 | likely pathogenic | Leukodystrophy; Status epilepticus; Global developmental delay; Seizure; Fetal growth restriction; EEG abnormality; Nystagmus; Hemiparesis; Strabismus; Progressive visual loss; Amblyopia; Small for gestational age; Breech presentation; Neonatal hypoglycemia; Developmental regression; Loss of ambulation; EMG abnormality; EMG: axonal abnormality; Dysmyelinating leukodystrophy | 2015-10-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588587 | SCV000695673 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2016-11-08 | criteria provided, single submitter | clinical testing | Variant summary: The GALC c.850G>A (p.Gly284Ser) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/120666 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361). This variant has been reported in multiple affected individuals with evidence of co-segregation. Functional assay showed variant with 5% of WT activity (De Gasperi et al 1996). Taken together, this variant is classified as pathogenic. |
Centre for Mendelian Genomics, |
RCV000588587 | SCV001369176 | likely pathogenic | Galactosylceramide beta-galactosidase deficiency | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. |
Invitae | RCV000588587 | SCV001416954 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 284 of the GALC protein (p.Gly284Ser). This variant is present in population databases (rs377274761, gnomAD 0.002%). This missense change has been observed in individual(s) with Krabbe disease or its clinical features (PMID: 8940268, 22520351, 29286531). It has also been observed to segregate with disease in related individuals. This variant is also known as p.G268S. ClinVar contains an entry for this variant (Variation ID: 374024). 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. Experimental studies have shown that this missense change affects GALC function (PMID: 8940268, 27638593). For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV001785610 | SCV002021209 | pathogenic | not provided | 2021-04-14 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000588587 | SCV002581113 | likely pathogenic | Galactosylceramide beta-galactosidase deficiency | 2022-07-27 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000588587 | SCV000791856 | likely pathogenic | Galactosylceramide beta-galactosidase deficiency | 2017-05-25 | no assertion criteria provided | clinical testing |