Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000548222 | SCV000626518 | uncertain significance | Glycogen storage disease, type II | 2021-06-04 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a GAA-related disease. This sequence change replaces glutamic acid with lysine at codon 50 of the GAA protein (p.Glu50Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
Center for Genomics, |
RCV000548222 | SCV003919994 | uncertain significance | Glycogen storage disease, type II | 2021-03-30 | criteria provided, single submitter | clinical testing | GAA NM_000152.4 exon 2 p.Glu50Lys (c.148G>A): This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID:456382). This variant amino acid Lysine (Lys) is present in multiple species including the marmoset and the squirrel monkey, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |