ClinVar Miner

Submissions for variant NM_006267.5(RANBP2):c.4294G>A (p.Val1432Ile)

gnomAD frequency: 0.00005  dbSNP: rs1006499929
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001229685 SCV001402139 uncertain significance Familial acute necrotizing encephalopathy 2019-10-01 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1432 of the RANBP2 protein (p.Val1432Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). 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: "Possibly Damaging"; Align-GVGD: "Class C25". The isoleucine 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.
GeneDx RCV001760226 SCV001999842 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004032674 SCV004934401 uncertain significance not specified 2023-12-16 criteria provided, single submitter clinical testing The c.4294G>A (p.V1432I) alteration is located in exon 20 (coding exon 20) of the RANBP2 gene. This alteration results from a G to A substitution at nucleotide position 4294, causing the valine (V) at amino acid position 1432 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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