Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569991 | SCV000674730 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-04-26 | criteria provided, single submitter | clinical testing | The p.K289N variant (also known as c.867A>C), located in coding exon 9 of the RB1 gene, results from an A to C substitution at nucleotide position 867. The lysine at codon 289 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly 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. |
| Labcorp Genetics |
RCV001054663 | SCV001219010 | uncertain significance | Retinoblastoma | 2019-12-12 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 486292). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 289 of the RB1 protein (p.Lys289Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. |