ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1646A>G (p.His549Arg)

dbSNP: rs2138145592
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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 RCV002034255 SCV002317474 uncertain significance Retinoblastoma 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 549 of the RB1 protein (p.His549Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. 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 disruptive. 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.
Ambry Genetics RCV002391141 SCV002703784 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-30 criteria provided, single submitter clinical testing The p.H549R variant (also known as c.1646A>G), located in coding exon 17 of the RB1 gene, results from an A to G substitution at nucleotide position 1646. The histidine at codon 549 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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