ClinVar Miner

Submissions for variant NM_014845.5(FIG4):c.2200G>A (p.Glu734Lys) (rs372846619)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000216084 SCV000613296 uncertain significance not specified 2016-09-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488398 SCV000575491 uncertain significance not provided 2017-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000488398 SCV000279664 uncertain significance not provided 2015-12-16 criteria provided, single submitter clinical testing The E734K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The E734K 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. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000278522 SCV000459637 uncertain significance Charcot-Marie-Tooth disease type 4 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000352246 SCV000459638 uncertain significance Amyotrophic Lateral Sclerosis, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000278522 SCV000946713 uncertain significance Charcot-Marie-Tooth disease type 4 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 734 of the FIG4 protein (p.Glu734Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs372846619, ExAC 0.01%). This variant has not been reported in the literature in individuals with FIG4-related disease. ClinVar contains an entry for this variant (Variation ID: 234661). 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: "Tolerated"; 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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