Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001062609 | SCV001227423 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2022-08-24 | 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 not expected to disrupt TRPV4 protein function. ClinVar contains an entry for this variant (Variation ID: 857016). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792; Invitae). This variant is present in population databases (rs372583866, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 852 of the TRPV4 protein (p.Arg852Cys). |
Molecular Genetics Laboratory, |
RCV001173242 | SCV001336324 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV002276608 | SCV002567113 | uncertain significance | Connective tissue disorder | 2022-03-17 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003433006 | SCV004117011 | uncertain significance | TRPV4-related condition | 2023-02-27 | criteria provided, single submitter | clinical testing | The TRPV4 c.2554C>T variant is predicted to result in the amino acid substitution p.Arg852Cys. This variant was reported as a variant of uncertain significance in an individual with Charcot-Marie-Tooth disease (Table S2 - Volodarsky et al. 2021. PubMed ID: 32376792). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-110221488-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |