Submissions for variant NG_009060.1(LDLR):g.4976CTC[2]

dbSNP: rs1270618112

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000505217	SCV005375290	uncertain significance	Hypercholesterolemia, familial, 1	2023-04-28	reviewed by expert panel	curation	The NM_000527.5 (LDLR):c.-187_185del variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PS3_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 April 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD version 2.1.1). PS3_Supporting: Level 3 experiment, heterologous cells (HepG2) were used for luciferase assays, 8% reporter gene expression observed, PMID 9610768 (Peeters et al., 1998).
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505217	SCV000599296	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Labcorp Genetics (formerly Invitae), Labcorp	RCV001360067	SCV001555963	uncertain significance	Familial hypercholesterolemia	2021-12-18	criteria provided, single submitter	clinical testing	This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 9610768). This variant is also known as -92 (FH-Pedi-2). ClinVar contains an entry for this variant (Variation ID: 438314). Studies have shown that this variant alters LDLR gene expression (PMID: 9610768). 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.
All of Us Research Program, National Institutes of Health	RCV000505217	SCV004834517	uncertain significance	Hypercholesterolemia, familial, 1	2024-01-11	criteria provided, single submitter	clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000505217	SCV000605982	pathogenic	Hypercholesterolemia, familial, 1		no assertion criteria provided	research