ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1376C>T (p.Ser459Phe)

dbSNP: rs1593455667
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822868 SCV000963690 uncertain significance Retinoblastoma 2023-12-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 459 of the RB1 protein (p.Ser459Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 664716). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 protein function. 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.
Ambry Genetics RCV001011230 SCV001171528 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-17 criteria provided, single submitter clinical testing The p.S459F variant (also known as c.1376C>T), located in coding exon 14 of the RB1 gene, results from a C to T substitution at nucleotide position 1376. The serine at codon 459 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002487851 SCV002784398 uncertain significance Bone osteosarcoma; Malignant tumor of urinary bladder; Small cell lung carcinoma; Retinoblastoma 2022-05-24 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000822868 SCV004831281 uncertain significance Retinoblastoma 2023-04-27 criteria provided, single submitter clinical testing

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