Submissions for variant NM_000321.3(RB1):c.2235AGA[1] (p.Glu748del)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004017167	SCV004844728	uncertain significance	Retinoblastoma	2023-10-02	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of glutamic acid at position 748 in the RB1 protein. 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 been identified in 1/249754 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV004017167	SCV005778522	uncertain significance	Retinoblastoma	2024-05-23	criteria provided, single submitter	clinical testing	This variant, c.2238_2240del, results in the deletion of 1 amino acid(s) of the RB1 protein (p.Glu748del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RB1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.