ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2539A>G (p.Lys847Glu)

dbSNP: rs2138358973
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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 RCV001369387 SCV001565825 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 lysine with glutamic acid at codon 847 of the RB1 protein (p.Lys847Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid.
Baylor Genetics RCV003462936 SCV004208541 uncertain significance Malignant tumor of urinary bladder 2023-06-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001369387 SCV004828359 uncertain significance Retinoblastoma 2023-05-30 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 847 of the RB1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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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