ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.664_681dup18 (p.Asp227_Glu228insCysLysAspLysSerAsp)

dbSNP: rs387906306
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001201377 SCV000285033 pathogenic Familial hypercholesterolemia 2022-01-10 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: 3733). This variant is also known as p.201-206dup and CKDKSD206–207ins. This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 7581403, 7649546, 10978268, 20145306). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs387906306, gnomAD 0.0009%). This variant, c.664_681dup, results in the insertion of 6 amino acid(s) of the LDLR protein (p.Cys222_Asp227dup), but otherwise preserves the integrity of the reading frame.
LDLR-LOVD, British Heart Foundation RCV000003931 SCV000294867 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II RCV000003931 SCV001653599 likely pathogenic Hypercholesterolemia, familial, 1 2021-05-24 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003457636 SCV004185153 likely pathogenic not provided 2023-11-01 criteria provided, single submitter clinical testing LDLR: PM2, PM4, PS2:Moderate, PS4:Moderate
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000003931 SCV004848338 likely pathogenic Hypercholesterolemia, familial, 1 2020-04-16 criteria provided, single submitter clinical testing The p.Cys222_Asp227dup variant in LDLR (also known as FH Padua-4l) has been reported in 5 families with hypercholesterolemia, occured de novo in 1 of these individuals, and segregated with disease in at least 1 affected relative (Bertolini 2000, Chmara 2010, Giesel 1995, Kotze 1995, Pavanello 2019). This variant has also been identified in 1/12968 of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID 3733). This variant is an insertion of 6 amino acids at position 222 and is not predicted to alter the protein reading-frame. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant hypercholesterolemia. ACMG/AMP Criteria applied: PM6, PM2, PS4_Moderate.
OMIM RCV000003931 SCV000024096 pathogenic Hypercholesterolemia, familial, 1 1995-01-01 no assertion criteria provided literature only
Natera, Inc. RCV001201377 SCV002086379 pathogenic Familial hypercholesterolemia 2021-05-07 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.