Submissions for variant NM_000321.3(RB1):c.380+10C>G

gnomAD frequency: 0.00158  dbSNP: rs187110786

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078640	SCV000110496	benign	not specified	2013-09-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231569	SCV000284625	benign	Retinoblastoma	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000231569	SCV000384535	benign	Retinoblastoma	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000078640	SCV000530091	likely benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Mendelics	RCV000231569	SCV001139306	likely benign	Retinoblastoma	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001727560	SCV001473229	likely benign	not provided	2023-08-09	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001727560	SCV002009254	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257403	SCV002530848	benign	Hereditary cancer-predisposing syndrome	2020-11-11	criteria provided, single submitter	curation
Ambry Genetics	RCV002257403	SCV002620161	likely benign	Hereditary cancer-predisposing syndrome	2016-01-04	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.
CeGaT Center for Human Genetics Tuebingen	RCV001727560	SCV003917284	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	RB1: BS1
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000231569	SCV004017263	benign	Retinoblastoma	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000078640	SCV001807839	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727560	SCV001968716	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751257	SCV005351929	likely benign	RB1-related disorder	2024-05-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).