Submissions for variant NM_000321.3(RB1):c.791C>G (p.Ala264Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002416717	SCV002677026	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-23	criteria provided, single submitter	clinical testing	The p.A264G variant (also known as c.791C>G), located in coding exon 8 of the RB1 gene, results from a C to G substitution at nucleotide position 791. The alanine at codon 264 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003514566	SCV004301394	uncertain significance	Retinoblastoma	2023-07-08	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1761213). 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. 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. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 264 of the RB1 protein (p.Ala264Gly). This variant is not present in population databases (gnomAD no frequency).