Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001326175 | SCV001517189 | uncertain significance | Aortic valve disease 2 | 2022-10-21 | 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 TBX5 protein function. ClinVar contains an entry for this variant (Variation ID: 1025814). This variant has not been reported in the literature in individuals affected with TBX5-related conditions. This variant is present in population databases (rs755152246, gnomAD 0.009%). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 425 of the TBX5 protein (p.His425Asn). |
Ambry Genetics | RCV002377420 | SCV002684826 | uncertain significance | Cardiovascular phenotype | 2022-08-03 | criteria provided, single submitter | clinical testing | The c.1273C>A (p.H425N) alteration is located in exon 9 (coding exon 8) of the TBX5 gene. This alteration results from a C to A substitution at nucleotide position 1273, causing the histidine (H) at amino acid position 425 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |