Submissions for variant NM_000321.3(RB1):c.1883C>T (p.Ala628Val)

dbSNP: rs1329826610

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000802384	SCV000942211	likely benign	Retinoblastoma	2025-01-18	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000802384	SCV004840821	uncertain significance	Retinoblastoma	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 628 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 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	RCV004028105	SCV005034554	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-15	criteria provided, single submitter	clinical testing	The p.A628V variant (also known as c.1883C>T), located in coding exon 19 of the RB1 gene, results from a C to T substitution at nucleotide position 1883. The alanine at codon 628 is replaced by valine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.