ClinVar Miner

Submissions for variant NM_001371279.1(REEP1):c.10T>G (p.Trp4Gly)

gnomAD frequency: 0.00001  dbSNP: rs863224189
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
GeneDx RCV000195547 SCV000252190 uncertain significance not provided 2014-11-10 criteria provided, single submitter clinical testing p.Trp4Gly (TGG>GGG): c.10 T>G in exon 1 of the REEP1 gene (*NM_022912.2) The W4G variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 3,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The W4G variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in NEUROPATHY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000641687 SCV000763334 uncertain significance Hereditary spastic paraplegia 31 2023-03-02 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 215086). This variant has not been reported in the literature in individuals affected with REEP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 4 of the REEP1 protein (p.Trp4Gly). 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. 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.
PreventionGenetics, part of Exact Sciences RCV004755809 SCV005365899 uncertain significance REEP1-related disorder 2024-03-06 no assertion criteria provided clinical testing The REEP1 c.2T>G variant is predicted to disrupt the translation initiation site (Start loss). This variant was reported in an individual with mental decline, gait anomalies, muscle anomalies, and positive Babinski sign (Case 13, Table 1, Cui et al. 2020. PubMed ID: 32501971). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. 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.