ClinVar Miner

Submissions for variant NM_000445.5(PLEC):c.10579C>T (p.Arg3527Cys) (rs200541837)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000177690 SCV000229602 likely benign not specified 2017-06-15 criteria provided, single submitter clinical testing
GeneDx RCV000177690 SCV000730335 likely benign not specified 2017-11-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000537688 SCV000650139 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 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 3527 of the PLEC protein (p.Arg3527Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs200541837, ExAC 0.2%). This variant has been reported heterozygous in two individuals from a single family affected with epidermolysis bullosa simplex (PMID: 23774525).  Neither of these individuals had symptoms consistent with muscular dystrophy.  ClinVar contains an entry for this variant (Variation ID: 196819). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It is not expected to cause disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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