ClinVar Miner

Submissions for variant NM_000445.5(PLEC):c.4729C>T (p.Arg1577Trp) (rs560918806)

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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 RCV000727716 SCV000855067 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing
GeneDx RCV000727716 SCV000620743 uncertain significance not provided 2018-08-15 criteria provided, single submitter clinical testing The R1577W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1577W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, most reported pathogenic variants in the PLEC gene are truncating/loss-of-function.
Invitae RCV000810249 SCV000950442 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 2018-08-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1577 of the PLEC protein (p.Arg1577Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs560918806, ExAC 0.08%). This variant has not been reported in the literature in individuals with PLEC-related disease. ClinVar contains an entry for this variant (Variation ID: 451973). 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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