ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.694G>T (p.Ala232Ser) (rs72658857)

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
Invitae RCV001213184 SCV001384802 uncertain significance Familial hypercholesterolemia 2019-10-04 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 232 of the LDLR protein (p.Ala232Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant also falls at the last nucleotide of exon 4 of the LDLR coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family with clinical features of heterozygous familial hypercholesterolemia (PMID: 31106925). However, another variant was also identified in LDLR in that family. This variant has been reported not to substantially affect LDLR protein function (PMID: 31106925). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Department of Genetics of Metabolic Diseases, Institute of Medical & Molecular Genetics,Hospital Universitario Hospital La Paz RCV000850043 SCV000992182 likely benign Familial hypercholesterolemia 1 2019-01-01 no assertion criteria provided 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.