ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2033A>G (p.His678Arg)

dbSNP: rs201046651
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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 RCV000687177 SCV000814730 uncertain significance Retinoblastoma 2021-07-12 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 678 of the RB1 protein (p.His678Arg). The histidine residue is moderately 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 with RB1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV002422474 SCV002718725 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-27 criteria provided, single submitter clinical testing The p.H678R variant (also known as c.2033A>G), located in coding exon 20 of the RB1 gene, results from an A to G substitution at nucleotide position 2033. The histidine at codon 678 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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.

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