ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.777T>G (p.Tyr259Ter)

dbSNP: rs2147228929
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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001553636 SCV001774569 likely pathogenic Familial hypercholesterolemia 2021-07-27 criteria provided, single submitter clinical testing Variant summary: LDLR c.777T>G (p.Tyr259X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251480 control chromosomes. c.777T>G has been reported in the literature without a specified genotype in at-least one individual from a cohort affected with Familial Hypercholesterolemia (example, Defeche_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001553636 SCV004271865 pathogenic Familial hypercholesterolemia 2023-06-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1192228). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 28964736). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr259*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073).

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.