ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.83C>G (p.Pro28Arg)

gnomAD frequency: 0.00001  dbSNP: rs776175164
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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 RCV000470650 SCV000551828 benign Retinoblastoma 2025-01-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV001017708 SCV001178831 likely benign Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV000470650 SCV005430171 uncertain significance Retinoblastoma 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 28 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 individuals affected with retinoblastoma in the literature (PMID: 30636860, 34277001), however in one of those patients the variant co-occurred with an RB1 duplication of exon 12, which more likely explains the disease phenotype (PMID: 34277001). This variant has been identified in 1/93876 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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