Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001947863 | SCV002189407 | uncertain significance | Aortic valve disease 2 | 2022-06-04 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 TBX5 protein function. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 299 of the TBX5 protein (p.Gly299Ser). This variant is present in population databases (rs201637366, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TBX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1416362). |
Ambry Genetics | RCV002370519 | SCV002683987 | likely benign | Cardiovascular phenotype | 2021-02-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
Revvity Omics, |
RCV003136304 | SCV003827076 | uncertain significance | Holt-Oram syndrome | 2019-11-12 | criteria provided, single submitter | clinical testing |