Submissions for variant NM_000321.3(RB1):c.1960+6T>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003112025	SCV003785090	uncertain significance	Retinoblastoma	2023-09-25	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 2417197). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 19 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.
All of Us Research Program, National Institutes of Health	RCV003112025	SCV004833676	uncertain significance	Retinoblastoma	2023-05-04	criteria provided, single submitter	clinical testing	This variant causes a T to C nucleotide substitution at the +6 position of intron 19 of the RB1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.