ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.773A>G (p.Asn258Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002625178 SCV003519911 uncertain significance Retinoblastoma 2022-08-18 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 258 of the RB1 protein (p.Asn258Ser).
Ambry Genetics RCV004072012 SCV005034576 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-13 criteria provided, single submitter clinical testing The p.N258S variant (also known as c.773A>G), located in coding exon 8 of the RB1 gene, results from an A to G substitution at nucleotide position 773. The asparagine at codon 258 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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.

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