Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001172889 | SCV001335964 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV002411666 | SCV002715130 | likely benign | Inborn genetic diseases | 2022-10-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV002559655 | SCV003446017 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2023-08-03 | 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. ClinVar contains an entry for this variant (Variation ID: 916858). This premature translational stop signal has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). This variant is present in population databases (rs545966662, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg616*) in the TRPV4 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TRPV4 cause disease. |