Submissions for variant NM_000321.3(RB1):c.1389+1G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002396599	SCV002699056	pathogenic	Hereditary cancer-predisposing syndrome	2024-01-12	criteria provided, single submitter	clinical testing	The c.1389+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 14 of the RB1 gene. This mutation was previously detected in an 18-month-old diagnosed with unilateral retinoblastoma; subsequent RNA studies showed that this alteration results in skipping of exon 14 (Houdayer C et al. Hum. Mutat. 2004 Feb;23:193-202; Houdayer C et al. Hum. Mutat. 2008 Jul;29:975-82). Of note, this mutation is also designated as IVS14+1G>A and g.76487G>A in published literature. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine	RCV004556855	SCV005046119	pathogenic	Retinoblastoma	2024-05-20	criteria provided, single submitter	clinical testing	Case and Pedigree Information: BILATERAL CASES:1, UNILATERAL CASES:1, TOTAL CASES:2, PEDIGREES:2. ACMG Codes Applied:PVS1, PM2