Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000543132 | SCV000629272 | uncertain significance | Retinoblastoma | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 392 of the RB1 protein (p.Ala392Thr). This variant is present in population databases (rs181988132, gnomAD 0.007%). 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: 458119). 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 | RCV001010134 | SCV001170285 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-02 | criteria provided, single submitter | clinical testing | The p.A392T variant (also known as c.1174G>A), located in coding exon 12 of the RB1 gene, results from a G to A substitution at nucleotide position 1174. The alanine at codon 392 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
| Fulgent Genetics, |
RCV002506302 | SCV002815355 | uncertain significance | Bone osteosarcoma; Malignant tumor of urinary bladder; Small cell lung carcinoma; Retinoblastoma | 2021-10-27 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003470731 | SCV004208525 | uncertain significance | Malignant tumor of urinary bladder | 2023-07-28 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000543132 | SCV004835513 | uncertain significance | Retinoblastoma | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 392 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has been identified in 1/250622 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |