ClinVar Miner

Submissions for variant NM_020549.5(CHAT):c.665G>C (p.Arg222Pro)

gnomAD frequency: 0.00086  dbSNP: rs8178989
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000711173 SCV000571157 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing The R222P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, nor was it observed with any significant frequency in the 1000 Genomes Project. The R222P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CHAT-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Genetic Services Laboratory, University of Chicago RCV000486523 SCV000594091 uncertain significance not specified 2016-06-10 criteria provided, single submitter clinical testing
Invitae RCV000555690 SCV000634136 likely benign Familial infantile myasthenia 2024-01-31 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000711173 SCV000841503 uncertain significance not provided 2018-02-16 criteria provided, single submitter clinical testing
Baylor Genetics RCV000555690 SCV001529244 uncertain significance Familial infantile myasthenia 2018-11-12 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002526613 SCV003707165 uncertain significance Inborn genetic diseases 2021-09-17 criteria provided, single submitter clinical testing The c.665G>C (p.R222P) alteration is located in exon 4 (coding exon 4) of the CHAT gene. This alteration results from a G to C substitution at nucleotide position 665, causing the arginine (R) at amino acid position 222 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000555690 SCV003833230 uncertain significance Familial infantile myasthenia 2023-12-20 criteria provided, single submitter clinical testing

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.