ClinVar Miner

Submissions for variant NM_000445.5(PLEC):c.8122G>A (p.Glu2708Lys) (rs200128670)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489095 SCV000577599 uncertain significance not specified 2016-10-10 criteria provided, single submitter clinical testing The E2708K variant in the PLEC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the E2708K variant is observed in 20/63530 (0.03%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The E2708K 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 in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E2708K as a variant of uncertain significance.
Invitae RCV000556369 SCV000650426 uncertain significance Epidermolysa bullosa simplex and limb girdle muscular dystrophy; Epidermolysis bullosa simplex, Ogna type; Epidermolysis bullosa simplex with pyloric atresia; Limb-girdle muscular dystrophy, type 2Q; Epidermolysis bullosa simplex with nail dystrophy 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 2708 of the PLEC protein (p.Glu2708Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs200128670, ExAC 0.03%). This variant has not been reported in the literature in individuals with PLEC-related disease. ClinVar contains an entry for this variant (Variation ID: 426994). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727773 SCV000855163 uncertain significance not provided 2017-11-27 criteria provided, single submitter clinical testing

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