ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.3656C>T (p.Thr1219Ile)

gnomAD frequency: 0.00004  dbSNP: rs768005049
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Robarts Research Institute, Western University RCV000660683 SCV000782849 uncertain significance Hypercholesterolemia, familial, 1 2018-01-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001838084 SCV001508346 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1219 of the APOB protein (p.Thr1219Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs768005049, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with APOB-related conditions. ClinVar contains an entry for this variant (Variation ID: 548053). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002458175 SCV002613928 uncertain significance Cardiovascular phenotype 2022-07-08 criteria provided, single submitter clinical testing The p.T1219I variant (also known as c.3656C>T), located in coding exon 23 of the APOB gene, results from a C to T substitution at nucleotide position 3656. The threonine at codon 1219 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.