Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Hudson |
RCV001526478 | SCV001736899 | uncertain significance | Severe achondroplasia-developmental delay-acanthosis nigricans syndrome | 2021-05-26 | criteria provided, single submitter | research | ACMG codes:PP3 |
Invitae | RCV002241569 | SCV002507593 | uncertain significance | not provided | 2021-03-30 | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FGFR3-related conditions. This variant is present in population databases (rs780415133, ExAC 0.01%). This sequence change replaces lysine with glutamic acid at codon 404 of the FGFR3 protein (p.Lys404Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |