ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.2087G>C (p.Arg696Pro) (rs137853022)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000006459 SCV000836445 pathogenic Familial dysautonomia 2018-02-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 696 of the IKBKAP protein (p.Arg696Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant is a rare pathogenic change among individuals of Ashkenazi Jewish ancestry affected with familial dysautonomia and has a carrier frequency of 1 in 1230 (0.08%) in this population (PMID:11179008, 11179021,12116234). ClinVar contains an entry for this variant (Variation ID: 6086). Experimental studies have shown that this missense change results in defective phosphorylation (PMID: 11179021). For these reasons, this variant has been classified as Pathogenic.
Myriad Women's Health, Inc. RCV000006459 SCV001193857 likely pathogenic Familial dysautonomia 2019-12-09 criteria provided, single submitter clinical testing NM_003640.3(IKBKAP):c.2087G>C(R696P) is classified as likely pathogenic in the context of familial dysautonomia. Sources cited for classification include the following: PMID 11179008 and 11179021. Classification of NM_003640.3(IKBKAP):c.2087G>C(R696P) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000006459 SCV000026642 pathogenic Familial dysautonomia 2002-07-01 no assertion criteria provided literature only
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000006459 SCV000734629 pathogenic Familial dysautonomia no assertion criteria provided clinical testing
Inherited Neuropathy Consortium RCV000789660 SCV000929032 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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.