ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1411C>T (p.Gln471Ter) (rs1354030520)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589929 SCV000696564 likely pathogenic Hereditary cancer-predisposing syndrome 2017-01-25 criteria provided, single submitter clinical testing Variant summary: The RB1 c.1411C>T (p.Gln471X) variant results in a premature termination codon, predicted to cause a truncated or absent RB1 protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. If this variant escapes NMD, it is expected to truncate Retinoblastoma-associated protein, A-box, Retinoblastoma-associated protein, B-box and Retinoblastoma-associated protein, C-terminal (via InterPro). Truncations downstream of this position have been classified as pathogenic clinical laboratories in ClinVar (e.g. p.Gln504Ter, p.Trp563Ter, p.Gln850Ter, etc.). This variant is absent in 24618 control chromosomes from ExAC. This variant has been reported in cell lines of one patient with acral melanoma in a published study (Bloethner_2008). In addition, in LOVD-RB database, this variant is reported as a germline variant in one RB patient and as a somatic variant in two RB patients. One reputable database (LOVD-RB) concludes its pathogenicity as pathogenic. Taken together, this variant is currently classified as 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.