ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1496G>A (p.Ser499Asn)

dbSNP: rs774706300
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001050300 SCV001214399 likely benign Retinoblastoma 2025-01-29 criteria provided, single submitter clinical testing
GeneDx RCV002286805 SCV002577300 uncertain significance not provided 2022-04-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002393246 SCV002700144 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-24 criteria provided, single submitter clinical testing The p.S499N variant (also known as c.1496G>A), located in coding exon 16 of the RB1 gene, results from a G to A substitution at nucleotide position 1496. The serine at codon 499 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly 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 RCV001050300 SCV004844676 uncertain significance Retinoblastoma 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 499 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 not been reported in individuals affected with RB1-related disorders in the literature. This variant has been identified in 1/245720 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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