Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023539 | SCV001185438 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-25 | criteria provided, single submitter | clinical testing | The p.A17V variant (also known as c.50C>T), located in coding exon 1 of the RB1 gene, results from a C to T substitution at nucleotide position 50. The alanine at codon 17 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved on limited sequence alignment. 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. |
| Invitae | RCV001862264 | SCV002311385 | uncertain significance | Retinoblastoma | 2021-01-29 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 825440). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with valine at codon 17 of the RB1 protein (p.Ala17Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. |