Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000815320 | SCV000955769 | uncertain significance | Retinoblastoma | 2023-03-15 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 658488). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 129 of the RB1 protein (p.His129Gln). 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 RB1 protein function. 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. |
| Ambry Genetics | RCV002363126 | SCV002624271 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | The p.H129Q variant (also known as c.387T>G), located in coding exon 4 of the RB1 gene, results from a T to G substitution at nucleotide position 387. The histidine at codon 129 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |