Submissions for variant NM_000321.3(RB1):c.2781G>T (p.Glu927Asp)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004017169	SCV004844776	uncertain significance	Retinoblastoma	2023-08-23	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with aspartic acid at codon 927 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 1/249684 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.
Ambry Genetics	RCV004661830	SCV005160505	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-26	criteria provided, single submitter	clinical testing	The p.E927D variant (also known as c.2781G>T), located in coding exon 27 of the RB1 gene, results from a G to T substitution at nucleotide position 2781. The glutamic acid at codon 927 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.