ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.238A>G (p.Lys80Glu)

gnomAD frequency: 0.00001  dbSNP: rs751870680
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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 RCV000456691 SCV000551806 benign Retinoblastoma 2024-09-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015371 SCV001176196 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-18 criteria provided, single submitter clinical testing The p.K80E variant (also known as c.238A>G), located in coding exon 2 of the RB1 gene, results from an A to G substitution at nucleotide position 238. The lysine at codon 80 is replaced by glutamic acid, an amino acid with similar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole-exome sequencing; this patient was diagnosed with Ewing's sarcoma (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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 RCV000456691 SCV004832012 uncertain significance Retinoblastoma 2024-09-27 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 80 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 been reported in a pediatric individual affected with Ewing's sarcoma (PMID: 26580448). This variant has been identified in 2/251344 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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