Submissions for variant NM_000321.3(RB1):c.534C>G (p.Ser178Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003627976	SCV004489482	uncertain significance	Retinoblastoma	2022-12-11	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RB1 protein function. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 178 of the RB1 protein (p.Ser178Arg).
Ambry Genetics	RCV004371704	SCV005034571	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-30	criteria provided, single submitter	clinical testing	The p.S178R variant (also known as c.534C>G), located in coding exon 5 of the RB1 gene, results from a C to G substitution at nucleotide position 534. The serine at codon 178 is replaced by arginine, an amino acid with 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.