ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.920C>T (p.Thr307Ile)

gnomAD frequency: 0.00079  dbSNP: rs183898408
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000989112 SCV000284633 benign Retinoblastoma 2021-12-17 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000121926 SCV000303589 benign not specified criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000121926 SCV000540158 likely benign not specified 2016-04-25 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: Frequency too high for disease; ExAC: 0.6% (51/8986) South Asian, 0.2% European
Ambry Genetics RCV000492127 SCV000580793 likely benign Hereditary cancer-predisposing syndrome 2019-04-11 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign);Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;Subpopulation frequency in support of benign classification
GeneDx RCV001719890 SCV000729718 likely benign not provided 2018-07-23 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28193182, 26107153, 20981092, 26332594, 26764160, 20090211, 24791139, 27181684, 27882345, 26396485, 17996702, 16343894, 25735316, 12541220, 24728327, 28780672, 33456302)
Mendelics RCV000989112 SCV001139311 benign Retinoblastoma 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000989112 SCV001267166 benign Retinoblastoma 2018-09-12 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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000121926 SCV001363519 benign not specified 2019-04-11 criteria provided, single submitter clinical testing Variant summary: RB1 c.920C>T (p.Thr307Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 223688 control chromosomes, predominantly at a frequency of 0.0048 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 115 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 a benign polymorphism found primarily in populations of South Asian origin. The variant, c.920C>T has been reported in the literature in individuals affected with Retinoblastoma (e.g. Brichard_2006, He_2014, Li_2016). Co-occurrences with other pathogenic variant(s) have been reported (RB1 c.871_872delGT), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory,University of Chicago RCV000121926 SCV002068032 likely benign not specified 2022-01-11 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000492127 SCV002530867 benign Hereditary cancer-predisposing syndrome 2020-10-08 criteria provided, single submitter curation
ITMI RCV000121926 SCV000086131 not provided not specified 2013-09-19 no assertion provided reference population

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