Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Immunology, |
RCV000611350 | SCV000583985 | likely pathogenic | 3-Methylglutaconic aciduria type 2 | criteria provided, single submitter | clinical testing | ||
Gene |
RCV000523344 | SCV000620386 | uncertain significance | not provided | 2017-09-13 | criteria provided, single submitter | clinical testing | The K264E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K264E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K264E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000611350 | SCV000758745 | uncertain significance | 3-Methylglutaconic aciduria type 2 | 2022-11-03 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 264 of the TAZ protein (p.Lys264Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Barth syndrome (PMID: 29077208). This variant is also known as c.658A>G; p.Lys220Glu. ClinVar contains an entry for this variant (Variation ID: 430910). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |