ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1960G>A (p.Val654Met)

dbSNP: rs483352690
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001854505 SCV002121401 pathogenic Retinoblastoma 2021-09-16 criteria provided, single submitter clinical testing This variant disrupts the c.1960G nucleotide in the RB1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 12541220, 15605413, 18181215, 21615945, 28606269). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 100808). This missense change has been observed in individual(s) with retinoblastoma (PMID: 14722923, 15884040, 22084214, 26925970, 29568217). It has also been observed in individuals without personal history of RB1-related conditions (PMID:29568217, 22084214, 26925970, 14722923). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 654 of the RB1 protein (p.Val654Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant also falls at the last nucleotide of exon 19, which is part of the consensus splice site for this exon.
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine RCV001854505 SCV005046227 pathogenic Retinoblastoma 2024-05-20 criteria provided, single submitter clinical testing Case and Pedigree Information: BILATERAL CASES:0, UNILATERAL CASES:2, TOTAL CASES:2, PEDIGREES:1. ACMG Codes Applied:PVS1, PM2
Richard Lifton Laboratory, Yale University School of Medicine RCV000087166 SCV000120028 unknown not provided flagged submission not provided Converted during submission to Uncertain significance.
Richard Lifton Laboratory, Yale University School of Medicine RCV000087166 SCV000155131 probable-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.