ClinVar Miner

Submissions for variant NM_006267.5(RANBP2):c.1535C>T (p.Pro512Leu)

gnomAD frequency: 0.00014  dbSNP: rs377029115
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000435639 SCV000511736 uncertain significance not provided 2016-12-30 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000802922 SCV000942771 uncertain significance Familial acute necrotizing encephalopathy 2020-10-07 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 missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with RANBP2-related disease. ClinVar contains an entry for this variant (Variation ID: 377321). This variant is present in population databases (rs377029115, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This sequence change replaces proline with leucine at codon 512 of the RANBP2 protein (p.Pro512Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
Fulgent Genetics, Fulgent Genetics RCV000802922 SCV002782146 uncertain significance Familial acute necrotizing encephalopathy 2021-11-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV004022282 SCV003865155 uncertain significance not specified 2023-02-22 criteria provided, single submitter clinical testing The c.1535C>T (p.P512L) alteration is located in exon 11 (coding exon 11) of the RANBP2 gene. This alteration results from a C to T substitution at nucleotide position 1535, causing the proline (P) at amino acid position 512 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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