ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1436A>G (p.Asp479Gly)

dbSNP: rs2138142793
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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 RCV002015453 SCV002277797 uncertain significance Retinoblastoma 2022-01-13 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RB1 protein function. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 479 of the RB1 protein (p.Asp479Gly).
All of Us Research Program, National Institutes of Health RCV002015453 SCV004840061 uncertain significance Retinoblastoma 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 479 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 not been identified 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.
Ambry Genetics RCV004045487 SCV005034488 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-09 criteria provided, single submitter clinical testing The p.D479G variant (also known as c.1436A>G), located in coding exon 16 of the RB1 gene, results from an A to G substitution at nucleotide position 1436. The aspartic acid at codon 479 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004571931 SCV005054157 uncertain significance Malignant tumor of urinary bladder 2023-11-08 criteria provided, single submitter clinical testing

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