Submissions for variant NM_000321.3(RB1):c.1736G>A (p.Arg579Gln)

gnomAD frequency: 0.00001  dbSNP: rs751560923

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000477144	SCV000551820	uncertain significance	Retinoblastoma	2023-12-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 579 of the RB1 protein (p.Arg579Gln). This variant is present in population databases (rs751560923, gnomAD 0.01%). 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: 410936). 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 with a negative predictive value of 80%. 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	RCV001012950	SCV001173473	likely benign	Hereditary cancer-predisposing syndrome	2022-02-03	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.
Baylor Genetics	RCV003463953	SCV004208513	uncertain significance	Malignant tumor of urinary bladder	2023-08-30	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000477144	SCV004844694	likely benign	Retinoblastoma	2023-06-08	criteria provided, single submitter	clinical testing
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine	RCV000477144	SCV005046191	uncertain significance	Retinoblastoma	2024-05-20	criteria provided, single submitter	clinical testing	Case and Pedigree Information: BILATERAL CASES:0, UNILATERAL CASES:1, TOTAL CASES:1, PEDIGREES:1. ACMG Codes Applied: