Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658421 | SCV000780193 | uncertain significance | not provided | 2018-05-30 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PLEC gene. The R2432C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R2432C variant is observed in 2/14948 (0.01%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The R2432C 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Labcorp Genetics |
RCV001203448 | SCV001374614 | 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 | 2023-08-31 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 546528). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs782579294, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2432 of the PLEC protein (p.Arg2432Cys). |
Revvity Omics, |
RCV000658421 | SCV003815602 | uncertain significance | not provided | 2019-02-27 | criteria provided, single submitter | clinical testing |