ClinVar Miner

Submissions for variant NM_020751.3(COG6):c.1961C>T (p.Thr654Met)

gnomAD frequency: 0.00003  dbSNP: rs747232819
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693190 SCV000821049 uncertain significance COG6-ongenital disorder of glycosylation; Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 654 of the COG6 protein (p.Thr654Met). This variant is present in population databases (rs747232819, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with COG6-related conditions. ClinVar contains an entry for this variant (Variation ID: 571928). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COG6 protein function with a negative predictive value of 80%. 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.