ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1453T>C (p.Ser485Pro)

dbSNP: rs1948522903
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053356 SCV001217614 uncertain significance Retinoblastoma 2019-02-02 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 485 of the RB1 protein (p.Ser485Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). 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.
All of Us Research Program, National Institutes of Health RCV001053356 SCV004843541 uncertain significance Retinoblastoma 2023-10-23 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 485 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 not been identified 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.
Ambry Genetics RCV004659316 SCV005160570 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-25 criteria provided, single submitter clinical testing The p.S485P variant (also known as c.1453T>C), located in coding exon 16 of the RB1 gene, results from a T to C substitution at nucleotide position 1453. The serine at codon 485 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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