Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000329690 | SCV000334516 | uncertain significance | not provided | 2017-10-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001369037 | SCV001565465 | 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 | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1177 of the PLEC protein (p.Arg1177Gln). This variant is present in population databases (rs782638887, gnomAD 0.06%). 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: 282840). 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. |
Ambry Genetics | RCV002519122 | SCV003723050 | uncertain significance | Inborn genetic diseases | 2022-06-09 | criteria provided, single submitter | clinical testing | The c.3530G>A (p.R1177Q) alteration is located in exon 28 (coding exon 27) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 3530, causing the arginine (R) at amino acid position 1177 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000329690 | SCV003811034 | uncertain significance | not provided | 2020-10-27 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004737406 | SCV005353819 | uncertain significance | PLEC-related disorder | 2024-05-16 | no assertion criteria provided | clinical testing | The PLEC c.3530G>A variant is predicted to result in the amino acid substitution p.Arg1177Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.054% of alleles in individuals of Latino descent in gnomAD, which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |