Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000799568 | SCV000939238 | 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 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 4463 of the PLEC protein (p.Thr4463Ile). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 645486). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PLEC protein function. 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, |
RCV003133621 | SCV003817259 | uncertain significance | not provided | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004028003 | SCV005006539 | uncertain significance | Inborn genetic diseases | 2024-01-24 | criteria provided, single submitter | clinical testing | The c.13388C>T (p.T4463I) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 13388, causing the threonine (T) at amino acid position 4463 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |