ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.148G>C (p.Glu50Gln)

gnomAD frequency: 0.00001  dbSNP: rs1060503085
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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 RCV000461996 SCV000551821 uncertain significance Retinoblastoma 2022-11-25 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 410937). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 50 of the RB1 protein (p.Glu50Gln).
Ambry Genetics RCV002393152 SCV002698969 likely benign Hereditary cancer-predisposing syndrome 2021-07-15 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 RCV000461996 SCV004847075 uncertain significance Retinoblastoma 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glutamine at codon 50 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 2/31388 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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