ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2603C>T (p.Pro868Leu)

dbSNP: rs769539980
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001954699 SCV002196036 uncertain significance Retinoblastoma 2021-04-05 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C35"). This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is present in population databases (rs769539980, ExAC 0.001%). This sequence change replaces proline with leucine at codon 868 of the RB1 protein (p.Pro868Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine.
All of Us Research Program, National Institutes of Health RCV001954699 SCV004826378 uncertain significance Retinoblastoma 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 868 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 1/251336 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.

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