Submissions for variant NM_000321.3(RB1):c.929G>A (p.Gly310Glu)

gnomAD frequency: 0.00029  dbSNP: rs200844292

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000232627	SCV000284634	benign	Retinoblastoma	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000232627	SCV000384541	likely benign	Retinoblastoma	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000456021	SCV000540156	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1 paper in HGMD; ExAC: 0.3% Latino, 1 homozygote
Ambry Genetics	RCV000563177	SCV000674709	likely benign	Hereditary cancer-predisposing syndrome	2018-11-01	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
GeneDx	RCV000730555	SCV000729719	likely benign	not provided	2019-03-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25525159, 15884040, 22180099)
Mendelics	RCV000232627	SCV000838920	likely benign	Retinoblastoma	2018-07-02	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000730555	SCV000858301	uncertain significance	not provided	2017-11-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000563177	SCV002530868	likely benign	Hereditary cancer-predisposing syndrome	2021-09-16	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000730555	SCV003917285	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	RB1: BS1, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000456021	SCV003928938	likely benign	not specified	2023-04-18	criteria provided, single submitter	clinical testing	Variant summary: RB1 c.929G>A (p.Gly310Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00037 in 196856 control chromosomes. The observed variant frequency is approximately 8.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in RB1 causing Retinoblastoma phenotype (4.2e-05), strongly suggesting that the variant is benign. Although reported in the literature, to our knowledge, no penetrant association of c.929G>A in individuals affected with Retinoblastoma and no conclusive experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with a majority consensus as benign/likely benign (n=8) (VUS, n=2). Based on the evidence outlined above, the variant was classified as likely benign.
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000232627	SCV001432962	uncertain significance	Retinoblastoma	2020-08-22	no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000456021	SCV003839945	likely benign	not specified	2022-11-25	no assertion criteria provided	clinical testing