ClinVar Miner

Submissions for variant NM_000445.5(PLEC):c.3379G>C (p.Gly1127Arg) (rs201404741)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727066 SCV000617203 uncertain significance not provided 2018-11-29 criteria provided, single submitter clinical testing The G1127R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G1127R variant is observed in 18/22,466 (0.08%) alleles from individuals of African background (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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727066 SCV000705321 uncertain significance not provided 2017-01-09 criteria provided, single submitter clinical testing
Invitae RCV000812504 SCV000952819 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 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1127 of the PLEC protein (p.Gly1127Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs201404741, ExAC 0.2%). This variant has not been reported in the literature in individuals with PLEC-related disease. ClinVar contains an entry for this variant (Variation ID: 449285). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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