Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Undiagnosed Diseases Network, |
RCV001310229 | SCV001499841 | pathogenic | DONSON-related Meier-Gorlin syndrome | 2020-02-20 | criteria provided, single submitter | clinical testing | |
Bicknell laboratory, |
RCV001527360 | SCV001738340 | pathogenic | Meier-Gorlin syndrome | criteria provided, single submitter | research | ||
Labcorp Genetics |
RCV003718402 | SCV004517045 | uncertain significance | not provided | 2023-09-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 270 of the DONSON protein (p.Tyr270Cys). This variant is present in population databases (rs367904759, gnomAD 0.006%). This missense change has been observed in individual(s) with Meier-Gorlin syndrome (PMID: 31784481). ClinVar contains an entry for this variant (Variation ID: 1012223). 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 DONSON protein function. Experimental studies have shown that this missense change affects DONSON function (PMID: 31784481). 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. |