Submissions for variant NM_000321.3(RB1):c.545C>T (p.Ser182Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002349707	SCV002650525	uncertain significance	Hereditary cancer-predisposing syndrome	2020-02-24	criteria provided, single submitter	clinical testing	The p.S182F variant (also known as c.545C>T), located in coding exon 6 of the RB1 gene, results from a C to T substitution at nucleotide position 545. The serine at codon 182 is replaced by phenylalanine, an amino acid with highly dissimilar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV004005695	SCV004825025	uncertain significance	Retinoblastoma	2023-08-08	criteria provided, single submitter	clinical testing	This missense variant replaces serine with phenylalanine at codon 182 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.