Submissions for variant NM_000321.3(RB1):c.2325+5G>C

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003516357	SCV004297233	likely pathogenic	Retinoblastoma	2024-02-18	criteria provided, single submitter	clinical testing	This sequence change falls in intron 22 of the RB1 gene. It does not directly change the encoded amino acid sequence of the RB1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with retinoblastoma (PMID: 20090211). This variant is also known as IVS 22+5 g.162115G>C. 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. This variant disrupts the c.2325+5G nucleotide in the RB1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 1662795, 16269091, 24225018). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.