ClinVar Miner

Submissions for variant NM_014845.5(FIG4):c.2639T>A (p.Ile880Asn) (rs746915624)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414249 SCV000491811 uncertain significance not specified 2016-11-21 criteria provided, single submitter clinical testing The I880N variant in the FIG4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I880N variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I880N as a variant of uncertain significance.
Invitae RCV001061319 SCV001226057 uncertain significance Charcot-Marie-Tooth disease type 4 2019-02-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with asparagine at codon 880 of the FIG4 protein (p.Ile880Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. This variant is present in population databases (rs746915624, ExAC 0.001%). This variant has not been reported in the literature in individuals with FIG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 373232). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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