ClinVar Miner

Submissions for variant NM_016579.4(CD320):c.256GAG[2] (p.Glu88del)

dbSNP: rs150384171
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000224888 SCV000238758 benign not provided 2018-05-24 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20524213, 29040465, 29663633, 30041674, 22819238, 31180159, 31462756)
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000004499 SCV000267241 likely pathogenic Methylmalonic acidemia due to transcobalamin receptor defect 2016-03-18 criteria provided, single submitter reference population
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224888 SCV000280766 likely benign not provided 2016-02-02 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV000004499 SCV000676997 uncertain significance Methylmalonic acidemia due to transcobalamin receptor defect 2024-01-26 criteria provided, single submitter clinical testing This variant, c.262_264del, results in the deletion of 1 amino acid(s) of the CD320 protein (p.Glu88del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs150384171, gnomAD 1.4%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with methylmalonic aciduria (PMID: 20524213, 22819238, 29663633, 34978764; Invitae). ClinVar contains an entry for this variant (Variation ID: 203643). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CD320 function (PMID: 20524213, 27411955). 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.
Eurofins Ntd Llc (ga) RCV000224888 SCV000700738 other not provided 2017-03-15 criteria provided, single submitter clinical testing
Mendelics RCV000004499 SCV001140969 benign Methylmalonic acidemia due to transcobalamin receptor defect 2023-08-22 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003398922 SCV004105179 likely pathogenic CD320-related disorder 2023-04-20 criteria provided, single submitter clinical testing The CD320 c.262_264delGAG variant is predicted to result in an in-frame deletion (p.Glu88del). This variant has been reported in the homozygous or compound heterozygous state in patients with methylmalonic acidemia and homocysteinemia due to transcobalamin receptor deficiency (e.g., Quadros et al. 2010. PubMed ID: 20524213; Karth et al. 2012. PubMed ID: 22819238; Hannah-Shmouni et al. 2018. PubMed ID: 29663633; Pappas et al. 2022. PubMed ID: 34978764). Fibroblast cells from patients apparently homozygous for the CD320 c.262_264del (p.Glu88del) variant showed reduced uptake of holo-transcobalamin (holo-TC) as well as elevated levels of homocysteine and methylmalonic acid in culture medium (Quadros et al. 2010. PubMed ID: 20524213; Pangilinan et al. 2022. PubMed ID: 35107211). The c.262_264del variant has been reported in a large population database at an allele frequency of up to ~1.4%, which would be high for an autosomal recessive disorder with a severe phenotype (http://gnomad.broadinstitute.org/variant/19-8369918-ACTC-A). It should be noted, however, that most reported patients with transcobalamin receptor deficiency have been clinically asymptomatic. These data suggest that this may possibly be a benign biochemical phenotype, although the long-term outcome in these individuals is not currently well understood (Hannah-Shmouni et al. 2018. PubMed ID: 29663633). In summary, we classify the c.262_264del (p.Glu88del) variant as likely pathogenic for recessive transcobalamin receptor deficiency.
OMIM RCV000004499 SCV000024673 pathogenic Methylmalonic acidemia due to transcobalamin receptor defect 2010-08-01 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.