Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001326439 | SCV001517470 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glutamic acid at codon 545 of the GALC protein (p.Ala545Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with a positive newborn screening result for GALC-related disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001760417 | SCV001991070 | uncertain significance | not provided | 2019-06-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001326439 | SCV002093619 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2021-06-30 | no assertion criteria provided | clinical testing |