Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020984 | SCV001182541 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-06 | criteria provided, single submitter | clinical testing | The p.I124M variant (also known as c.372A>G), located in coding exon 3 of the RB1 gene, results from an A to G substitution at nucleotide position 372. The isoleucine at codon 124 is replaced by methionine, 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. |
| Labcorp Genetics |
RCV001301503 | SCV001490675 | uncertain significance | Retinoblastoma | 2022-07-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 824133). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 124 of the RB1 protein (p.Ile124Met). 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: "Deleterious"; PolyPhen-2: "Benign"; 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. |