ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1564A>C (p.Asn522His)

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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 RCV002819745 SCV003198178 uncertain significance Retinoblastoma 2022-05-27 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 histidine, which is basic and polar, at codon 522 of the RB1 protein (p.Asn522His).
Ambry Genetics RCV004661483 SCV005160565 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-31 criteria provided, single submitter clinical testing The p.N522H variant (also known as c.1564A>C), located in coding exon 17 of the RB1 gene, results from an A to C substitution at nucleotide position 1564. The asparagine at codon 522 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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