ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.6659T>C (p.Val2220Ala) (rs374736992)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520891 SCV000620067 uncertain significance not provided 2017-08-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the APOB gene. The V2220A variant has not been published as pathogenic or been reported as benign to our knowledge. The V2220A variant is observed in 4/64200 (0.006%) alleles from individuals of Non-Finnish European background in the Exome Aggregation Consortium (ExAC) dataset; no individuals were reported to be homozygous (Lek et al., 2016). The V2220A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved and alanine (A) is the wild-type amino acid at this position in multiple species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function.
Color RCV000775500 SCV000909864 uncertain significance Familial hypercholesterolemias 2018-10-10 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.Val2193Ala in the mature protein) is a missense variant located in the alpha 2 domain of the APOB protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant is rare in the general population and has been identified in 8/108940 Non-Finnish European chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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.