ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.761G>A (p.Arg254Lys)

gnomAD frequency: 0.00002  dbSNP: rs200674097
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000699465 SCV000828178 likely benign Retinoblastoma 2024-01-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV001026628 SCV001189049 likely benign Hereditary cancer-predisposing syndrome 2023-02-14 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.
Sema4, Sema4 RCV001026628 SCV002530863 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-24 criteria provided, single submitter curation
Baylor Genetics RCV003460960 SCV004208531 uncertain significance Malignant tumor of urinary bladder 2023-07-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000699465 SCV004844629 uncertain significance Retinoblastoma 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 254 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 3/282558 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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