Total submissions: 28
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000030134 | SCV002817169 | benign | Hypercholesterolemia, familial, 1 | 2022-05-24 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.2177C>T (p.Thr726Ile) variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes BA1 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1 - FAF = 0.008138 (0.8138%) in European (non-Finnish) exomes (gnomAD v2.1.1), so BA1 is Met. BP4 - REVEL = 0.454, it is below 0.50, so splicing evaluation is required. Functional data on splicing not available. A) variant not on limits B) does not create AG C) variant is exonic and there 1 an AG nearby MES scores: variant cryptic = -1.90, wt cryptic = -1.77, canonical acceptor = 8.76. Ratio variant cryptic/wt cryptic: -1.90/-1.77 = 1.07 --- it is not above 1.1 Ratio variant cryptic/canonical acceptor: -1.90/8.76 --- it is not above 0.9 --- BP4 is Met. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000247593 | SCV000052789 | benign | not specified | 2023-05-04 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.2177C>T (p.Thr726Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0055 in 251244 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in LDLR causing Familial Hypercholesterolemia phenotype (0.0013), strongly suggesting that the variant is benign. Twenty-one clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Institute for Integrative and Experimental Genomics, |
RCV000030134 | SCV000212141 | likely benign | Hypercholesterolemia, familial, 1 | criteria provided, single submitter | research | ||
LDLR- |
RCV000030134 | SCV000295909 | benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Genomic Diagnostic Laboratory, |
RCV000030134 | SCV000296927 | benign | Hypercholesterolemia, familial, 1 | 2015-07-20 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000247593 | SCV000304690 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Cardiovascular Research Group, |
RCV000030134 | SCV000323004 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | 1Hmz + 1Htz/100 normolipidemic individuals; 0/200 non-FH alleles |
Cardiovascular Biomarker Research Laboratory, |
RCV000030134 | SCV000323104 | likely benign | Hypercholesterolemia, familial, 1 | 2016-08-31 | criteria provided, single submitter | research | does not meet required criteria. "Little/No effect" on the LDL receptor activity based on experimental validation. |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000030134 | SCV000503472 | benign | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 17/Software predictions: Benign |
Molecular Genetics Laboratory, |
RCV000030134 | SCV000540902 | benign | Hypercholesterolemia, familial, 1 | 2017-03-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000771082 | SCV000556773 | benign | Familial hypercholesterolemia | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Laboratory of Genetics and Molecular Cardiology, |
RCV000030134 | SCV000588642 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Fundacion Hipercolesterolemia Familiar | RCV000030134 | SCV000607682 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Color Diagnostics, |
RCV000771082 | SCV000689774 | benign | Familial hypercholesterolemia | 2022-01-19 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000247593 | SCV000730513 | benign | not specified | 2017-07-10 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Iberoamerican FH Network | RCV000030134 | SCV000748059 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Robarts Research Institute, |
RCV000030134 | SCV000782936 | benign | Hypercholesterolemia, familial, 1 | 2018-01-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000162011 | SCV000888164 | benign | not provided | 2022-07-20 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000771082 | SCV000902622 | benign | Familial hypercholesterolemia | 2018-06-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000162011 | SCV001151672 | likely benign | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | LDLR: BS2 |
Illumina Laboratory Services, |
RCV000030134 | SCV001286052 | benign | Hypercholesterolemia, familial, 1 | 2018-04-10 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
ARUP Laboratories, |
RCV000162011 | SCV002048044 | benign | not provided | 2023-06-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002426526 | SCV002726703 | benign | Cardiovascular phenotype | 2017-11-13 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Dept. |
RCV000162011 | SCV000189586 | not provided | not provided | no assertion provided | in vitro | ||
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000030134 | SCV000606613 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000030134 | SCV000733831 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | clinical testing | ||
Natera, |
RCV000771082 | SCV001453900 | benign | Familial hypercholesterolemia | 2020-01-12 | no assertion criteria provided | clinical testing | |
Clinical Genetics, |
RCV000247593 | SCV001926111 | benign | not specified | no assertion criteria provided | clinical testing |