Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000705482 | SCV000834481 | uncertain significance | Retinoblastoma | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 339 of the RB1 protein (p.His339Arg). 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: 581603). 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. |
| Mendelics | RCV000705482 | SCV000838922 | uncertain significance | Retinoblastoma | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004026691 | SCV005034443 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-17 | criteria provided, single submitter | clinical testing | The p.H339R variant (also known as c.1016A>G), located in coding exon 10 of the RB1 gene, results from an A to G substitution at nucleotide position 1016. The histidine at codon 339 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV004773117 | SCV005386918 | uncertain significance | not provided | 2024-02-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23516486) |