ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1022A>G (p.Lys341Arg)

dbSNP: rs1393042716
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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 RCV001312830 SCV001503301 uncertain significance Retinoblastoma 2020-01-08 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 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 341 of the RB1 protein (p.Lys341Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine.
Ambry Genetics RCV002447323 SCV002679364 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-01 criteria provided, single submitter clinical testing The p.K341R variant (also known as c.1022A>G), located in coding exon 10 of the RB1 gene, results from an A to G substitution at nucleotide position 1022. The lysine at codon 341 is replaced by arginine, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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