ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.7514G>A (p.Arg2505Gln)

gnomAD frequency: 0.00003  dbSNP: rs782664854
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000321988 SCV000337570 uncertain significance not provided 2018-07-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000704318 SCV000833262 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 2022-08-16 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 284799). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs782664854, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2532 of the PLEC protein (p.Arg2532Gln).
Neuberg Centre For Genomic Medicine, NCGM RCV004771471 SCV005382538 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2Q 2023-05-20 criteria provided, single submitter clinical testing The observed missense c.7514G>A(p.Arg2505Gln) variant in PLEC gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Arg2505Gln variant has been reported with allele frequency of 0.004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance (multiple submissions). Computational evidences (Polyphen - Possibly damaging, SIFT - Damaging and MutationTaster - Polymorphism) predict conflicting evidence on protein structure and function for this variant. The amino acid change p.Arg2505Gln in PLEC is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 2505 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).
PreventionGenetics, part of Exact Sciences RCV004737414 SCV005353798 uncertain significance PLEC-related disorder 2024-05-06 no assertion criteria provided clinical testing The PLEC c.7595G>A variant is predicted to result in the amino acid substitution p.Arg2532Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.