ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.12739C>T (p.Gln4247Ter)

gnomAD frequency: 0.00001  dbSNP: rs907126709
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 RCV001838023 SCV000777020 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2022-08-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln4247*) in the APOB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 317 amino acid(s) of the APOB protein. This variant is present in population databases (no rsID available, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with hypercholesterolemia (PMID: 33418990). ClinVar contains an entry for this variant (Variation ID: 544074). This variant disrupts a region of the APOB protein in which other variant(s) (p.Tyr4380*) have been observed in individuals with APOB-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.
Illumina Laboratory Services, Illumina RCV000778588 SCV000914894 uncertain significance APOB-Related Disorders 2018-11-14 criteria provided, single submitter clinical testing The APOB c.12739C>T (p.Gln4247Ter) variant is a stop-gained variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is located in the last exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for APOB-related disorders.
AiLife Diagnostics, AiLife Diagnostics RCV002223901 SCV002501871 uncertain significance not provided 2021-08-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002369769 SCV002686039 uncertain significance Cardiovascular phenotype 2022-01-04 criteria provided, single submitter clinical testing The p.Q4247* variant (also known as c.12739C>T), located in coding exon 29 of the APOB gene, results from a C to T substitution at nucleotide position 12739. This changes the amino acid from a glutamine to a stop codon within coding exon 29. This alteration has been reported in a familial hypercholesterolemia (FH) cohort (Meshkov A et al. Genes (Basel), 2021 01;12:). This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of APOB has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001838023 SCV002776010 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2021-11-12 criteria provided, single submitter clinical testing

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.