Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586456 | SCV000696479 | uncertain significance | not provided | 2016-02-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000586456 | SCV001773646 | likely pathogenic | not provided | 2021-03-09 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Invitae | RCV001853980 | SCV002258578 | uncertain significance | Propionic acidemia | 2021-02-13 | criteria provided, single submitter | clinical testing | 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. 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 PCCA protein function. This variant has been observed in individual(s) with propionic acidemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 495792). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with lysine at codon 316 of the PCCA protein (p.Met316Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. |