Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000800264 | SCV000939967 | uncertain significance | Retinoblastoma | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 130 of the RB1 protein (p.Lys130Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 646052). 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 with a negative predictive value of 80%. 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 | RCV002360947 | SCV002624383 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The p.K130T variant (also known as c.389A>C), located in coding exon 4 of the RB1 gene, results from an A to C substitution at nucleotide position 389. The lysine at codon 130 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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. |