Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
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. |
| Eurofins Ntd Llc |
RCV000727066 | SCV000705321 | uncertain significance | not provided | 2017-01-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000812504 | SCV000952819 | uncertain significance | Epidermolysis bullosa simplex 5B, with muscular dystrophy; Epidermolysis bullosa simplex, Ogna type; Epidermolysis bullosa simplex 5C, with pyloric atresia; Autosomal recessive limb-girdle muscular dystrophy type 2Q; Epidermolysis bullosa simplex with nail dystrophy | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1127 of the PLEC protein (p.Gly1127Arg). This variant is present in population databases (rs201404741, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. ClinVar contains an entry for this variant (Variation ID: 449285). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLEC protein function with a negative predictive value of 80%. 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. |
| Revvity Omics, |
RCV000727066 | SCV003816720 | uncertain significance | not provided | 2022-06-13 | criteria provided, single submitter | clinical testing |