ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.897T>A (p.Phe299Leu)

gnomAD frequency: 0.00002  dbSNP: rs772362181
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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 RCV000812372 SCV000952683 uncertain significance Retinoblastoma 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 299 of the RB1 protein (p.Phe299Leu). This variant is present in population databases (rs772362181, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 656058). 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. 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.
Ambry Genetics RCV002370189 SCV002683802 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-15 criteria provided, single submitter clinical testing The c.897T>A (p.F299L) alteration is located in exon 9 (coding exon 9) of the RB1 gene. This alteration results from a T to A substitution at nucleotide position 897, causing the phenylalanine (F) at amino acid position 299 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV000812372 SCV004844636 uncertain significance Retinoblastoma 2023-12-07 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 299 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 hereditary cancer in the literature. This variant has been identified in 2/193242 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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