Submissions for variant NM_000527.5(LDLR):c.1658_1660del (p.Tyr553del)

dbSNP: rs1555806019

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780379	SCV000917582	uncertain significance	not specified	2023-02-13	criteria provided, single submitter	clinical testing	Variant summary: LDLR c.1658_1660delACT (p.Tyr553del) results in an in-frame deletion that is predicted to remove 1 amino acid from the LDLR class B repeat region (IPR000033) of the encoded protein. The variant was absent in 251464 control chromosomes. c.1658_1660delACT has been reported in the literature in individuals affected with Familial Hypercholesterolemia, including one individual with homozygous autosomal dominant hypercholesterolemia (Ten Kate_2013, Sjouke_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000508809	SCV000606476	pathogenic	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Natera, Inc.	RCV001275281	SCV001460281	uncertain significance	Familial hypercholesterolemia	2020-09-16	no assertion criteria provided	clinical testing