ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1543C>T (p.Pro515Ser)

dbSNP: rs866664638
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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 RCV001236727 SCV001409463 uncertain significance Retinoblastoma 2020-09-30 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 515 of the RB1 protein (p.Pro515Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.
Ambry Genetics RCV002402742 SCV002705915 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-13 criteria provided, single submitter clinical testing The p.P515S variant (also known as c.1543C>T), located in coding exon 17 of the RB1 gene, results from a C to T substitution at nucleotide position 1543. The proline at codon 515 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001236727 SCV004844681 uncertain significance Retinoblastoma 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 515 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.

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