Submissions for variant NM_000321.3(RB1):c.2356C>T (p.Pro786Ser)

gnomAD frequency: 0.00001  dbSNP: rs754507551

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000528489	SCV000629305	likely benign	Retinoblastoma	2024-01-24	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000761011	SCV000890926	uncertain significance	Medulloblastoma	2016-02-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001015131	SCV001175934	likely benign	Hereditary cancer-predisposing syndrome	2020-12-03	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	RCV000528489	SCV004844734	uncertain significance	Retinoblastoma	2024-01-11	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 786 of the RB1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 13/251436 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.
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine	RCV000528489	SCV005046311	uncertain significance	Retinoblastoma	2024-05-20	criteria provided, single submitter	clinical testing	Case and Pedigree Information: BILATERAL CASES:0, UNILATERAL CASES:2, TOTAL CASES:2, PEDIGREES:2. ACMG Codes Applied: