ClinVar Miner

Submissions for variant NM_012179.4(FBXO7):c.839T>C (p.Leu280Pro)

gnomAD frequency: 0.00004  dbSNP: rs776439796
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519913 SCV000620862 uncertain significance not provided 2017-09-14 criteria provided, single submitter clinical testing The L280P variant in the FBXO7 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L280P variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L280P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L280P as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001858020 SCV002183921 uncertain significance Parkinsonian-pyramidal syndrome 2022-07-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 280 of the FBXO7 protein (p.Leu280Pro). This variant is present in population databases (rs776439796, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FBXO7-related conditions. ClinVar contains an entry for this variant (Variation ID: 452085). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002525226 SCV003716804 uncertain significance Inborn genetic diseases 2022-05-01 criteria provided, single submitter clinical testing The c.839T>C (p.L280P) alteration is located in exon 5 (coding exon 5) of the FBXO7 gene. This alteration results from a T to C substitution at nucleotide position 839, causing the leucine (L) at amino acid position 280 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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