Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000809007 | SCV000949141 | uncertain significance | Retinoblastoma | 2020-02-02 | 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 tolerated, 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. 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 leucine with isoleucine at codon 44 of the RB1 protein (p.Leu44Ile). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and isoleucine. |
| Ambry Genetics | RCV002381794 | SCV002689999 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-25 | criteria provided, single submitter | clinical testing | The p.L44I variant (also known as c.130C>A), located in coding exon 1 of the RB1 gene, results from a C to A substitution at nucleotide position 130. The leucine at codon 44 is replaced by isoleucine, an amino acid with highly 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. |