ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1681C>T (p.Leu561Phe)

gnomAD frequency: 0.00001  dbSNP: rs761257231
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001220561 SCV001392558 uncertain significance Retinoblastoma 2023-08-31 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 561 of the RB1 protein (p.Leu561Phe). This variant is present in population databases (rs761257231, gnomAD 0.009%). 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: 949159). 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 not 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 RCV003163697 SCV003871119 likely benign Hereditary cancer-predisposing syndrome 2023-02-03 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 RCV001220561 SCV004839544 uncertain significance Retinoblastoma 2023-12-01 criteria provided, single submitter clinical testing

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