Submissions for variant NM_018972.4(GDAP1):c.556A>G (p.Ile186Val) (rs148508128)

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
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000416100	SCV000493443	uncertain significance	not provided	2016-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000416100	SCV000279436	uncertain significance	not provided	2016-03-22	criteria provided, single submitter	clinical testing	The I186V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I186V variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes Project. The I186V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000200426	SCV000255035	uncertain significance	Charcot-Marie-Tooth disease, type 4A	2018-12-14	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with valine at codon 186 of the GDAP1 protein (p.Ile186Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs148508128, ExAC 0.05%). This variant has not been reported in the literature in individuals with GDAP1-related disease. ClinVar contains an entry for this variant (Variation ID: 216707). 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. 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.