ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1167A>C (p.Leu389Phe)

dbSNP: rs1952784310
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001927984 SCV002179423 uncertain significance Retinoblastoma 2023-02-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 389 of the RB1 protein (p.Leu389Phe). This variant is not present in population databases (gnomAD no frequency). 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: 1410164). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV002331441 SCV002632714 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-08 criteria provided, single submitter clinical testing The p.L389F variant (also known as c.1167A>C), located in coding exon 12 of the RB1 gene, results from an A to C substitution at nucleotide position 1167. The leucine at codon 389 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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