ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.7132A>G (p.Met2378Val)

gnomAD frequency: 0.00001  dbSNP: rs79121794
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001211038 SCV001382559 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 2020-03-22 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PLEC-related conditions. This variant is present in population databases (rs79121794, ExAC 0.01%). This sequence change replaces methionine with valine at codon 2405 of the PLEC protein (p.Met2405Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine.
Ambry Genetics RCV002561748 SCV003529037 uncertain significance Inborn genetic diseases 2022-06-24 criteria provided, single submitter clinical testing The c.7213A>G (p.M2405V) alteration is located in exon 32 (coding exon 31) of the PLEC gene. This alteration results from a A to G substitution at nucleotide position 7213, causing the methionine (M) at amino acid position 2405 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV004771495 SCV005382537 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2Q 2023-05-20 criteria provided, single submitter clinical testing The observed missense c.7132A>G(p.Met2378Val) variant in PLEC gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Met2378Val variant has been reported with allele frequency of 0.001% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. Computational evidences (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predict conflicting evidence on protein structure and function for this variant. The amino acid change p.Met2378Val in PLEC is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Met at position 2378 is changed to a Val 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).

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.