Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000237075 | SCV000294065 | uncertain significance | not provided | 2024-09-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Labcorp Genetics |
RCV001035654 | SCV001198988 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2024-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 838 of the TRPV4 protein (p.Pro838Leu). This variant is present in population databases (rs140602150, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of TRPV4-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 246488). 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 not expected to disrupt TRPV4 protein function with a negative predictive value of 95%. 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. |