ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1318G>A (p.Glu440Lys)

gnomAD frequency: 0.00002  dbSNP: rs1060503078
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000466200 SCV000551807 benign Retinoblastoma 2024-01-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492148 SCV000580876 likely benign Hereditary cancer-predisposing syndrome 2018-11-02 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.
Baylor Genetics RCV003470478 SCV004208522 uncertain significance Malignant tumor of urinary bladder 2023-08-13 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000466200 SCV004844657 uncertain significance Retinoblastoma 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 440 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 an individual affected with bilateral retinoblastoma, but was also observed the the individual's unaffected mother (PMID: 32218800). This variant has been identified in 2/282426 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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