ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.818G>A (p.Arg273Gln) (rs879254192)

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 RCV000236133 SCV000293766 likely pathogenic not provided 2016-01-11 criteria provided, single submitter clinical testing The R273Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different amino acid substitution at the same position (R273G) has been previously reported in a patient with CMT4C who had another variant on the opposite allele (Kabzinska et al., 2010). R273Q was not observed in approximately 6,500 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 R273Q 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000236133 SCV000575562 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001066504 SCV001231517 uncertain significance Charcot-Marie-Tooth disease, type 4A 2019-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 273 of the GDAP1 protein (p.Arg273Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GDAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 246285). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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.