Submissions for variant NM_000321.3(RB1):c.2018A>G (p.His673Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004017165	SCV004844715	uncertain significance	Retinoblastoma	2023-06-26	criteria provided, single submitter	clinical testing	This missense variant replaces histidine with arginine at codon 673 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 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.
Ambry Genetics	RCV004372000	SCV005034348	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-08	criteria provided, single submitter	clinical testing	The p.H673R variant (also known as c.2018A>G), located in coding exon 20 of the RB1 gene, results from an A to G substitution at nucleotide position 2018. The histidine at codon 673 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.