ClinVar Miner

Submissions for variant NM_006363.6(SEC23B):c.40C>T (p.Arg14Trp) (rs121918222)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000153924 SCV000330039 pathogenic not provided 2016-10-10 criteria provided, single submitter clinical testing The R14W variant in the SEC23B gene has been reported previously in association with congenital dyserythropoietic anemia type II in multiple unrelated individuals when present with a second variant in the SEC23B gene (Bianchi et al., 2009; Schwarz et al., 2009; Satchwell et al., 2013). The R14W variant is one of the most common recurrent variants in the SEC23B gene and is considered a founder mutation in Italy, Morocco, and Israel (Russo et al., 2014). The R14W variant was not observed at any significant frequency in approximately 6500 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 R14W 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. This substitution occurs at a position that is not conserved. However, in vitro studies demonstrate that R14W-SEC23B is unstable with less than 5% of the protein detectable compared to wild type (Schwarz et al., 2009). Therefore, we interpret R14W as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153924 SCV000331589 pathogenic not provided 2015-08-26 criteria provided, single submitter clinical testing
Invitae RCV000688744 SCV000816367 pathogenic Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 2017-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 14 of the SEC23B protein (p.Arg14Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121918222, ExAC 0.04%). This variant is one of the most common variants identified in individuals with congenital dyserythropoietic anemia type II (PMID: 19561605, 19621418, 20015893, 21850656). ClinVar contains an entry for this variant (Variation ID: 1223). An experimental study has shown that this missense change results in <5% of the expression of wild-type protein (PMID: 19561605). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001282 SCV000021432 pathogenic Congenital dyserythropoietic anemia, type II 2009-09-01 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.