Submissions for variant NM_000321.3(RB1):c.1411C>T (p.Gln471Ter)

dbSNP: rs1354030520

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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.
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine	RCV004556806	SCV005046126	pathogenic	Retinoblastoma	2024-05-20	criteria provided, single submitter	clinical testing	Case and Pedigree Information: BILATERAL CASES:2, UNILATERAL CASES:0, TOTAL CASES:2, PEDIGREES:2. ACMG Codes Applied:PVS1, PM2