ClinVar Miner

Submissions for variant NM_006267.5(RANBP2):c.4981A>C (p.Met1661Leu)

gnomAD frequency: 0.00001  dbSNP: rs551971749
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001322325 SCV001513192 uncertain significance Familial acute necrotizing encephalopathy 2020-07-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 1661 of the RANBP2 protein (p.Met1661Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with RANBP2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. 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.

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