Total submissions: 26
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000210234 | SCV005688686 | uncertain significance | Hypercholesterolemia, familial, 1 | 2024-10-28 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.148G>T (p.Ala50Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying no ACMG/AMP evidence codes as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on October 28th, 2024. |
| All of Us Research Program, |
RCV000210234 | SCV005426432 | likely benign | Hypercholesterolemia, familial, 1 | 2024-09-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002390209 | SCV002698728 | likely benign | Cardiovascular phenotype | 2019-01-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000058916 | SCV002046748 | likely benign | not provided | 2022-07-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000058916 | SCV001812513 | likely benign | not provided | 2020-07-20 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 27044878, 30333156, 7820934, 20506408, 18325082, 16542394, 15576851, 10090484, 26332594, 25487149, 25637381, 22390909, 24055113) |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000058916 | SCV001433284 | uncertain significance | not provided | 2020-02-17 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000210234 | SCV001429403 | uncertain significance | Hypercholesterolemia, familial, 1 | 2019-02-04 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000210234 | SCV001281756 | likely benign | Hypercholesterolemia, familial, 1 | 2018-09-07 | 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000455660 | SCV000919594 | likely benign | not specified | 2025-04-18 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.148G>T (p.Ala50Ser; also known as p.Ala29Ser) results in a conservative amino acid change located in the first class A repeat domain (IPR002172) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00054 in 262944 control chromosomes, predominantly at a frequency of 0.00097 within the Non-Finnish European subpopulation in the gnomAD database. However, in certain European regions the variant was found with a higher allele frequency, e.g. in the Swedish (0.0018), which is higher than estimated maximum expected for a pathogenic variant in LDLR causing Familial Hypercholesterolemia (0.0013), suggesting that the variant might be benign. The variant, c.148G>T, has been reported in the literature in individuals affected with hypercholesterolemia, however it was also found in controls and individuals with low LDL cholesterol (Ahmad_2012, Beaudoin_2012, Brusgaard_2006, Chmarra_2010, Do_2015, Ebhardt_1999, Fouchier_2001, Jensen_1994, Junyent_2010, Koeijvoets_2005, Lange_2014, Leren_2004, Tejedor_2010, Geller_2018, Sustar_2022). These reports do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. In a family the variant was found to not segregate with disease (Jensen_1994). In addition, co-occurrences with other pathogenic variants have been reported (e.g. LDLR c.12G>A (p.Trp4X); Tejedor_2010 and LDLR c.1033C>T (p.Gln345X) in an internal LCA sample), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23064986, 22923420, 16542394, 20145306, 25487149, 24055113, 10090484, 11810272, 30333156, 7820934, 19717150, 15823280, 24507775, 15199436, 10735632, 24956927, 28145427, 35913489, 20428891). ClinVar contains an entry for this variant (Variation ID: 68099). Based on the evidence outlined above, the variant was classified as likely benign. |
| Color Diagnostics, |
RCV000776111 | SCV000910984 | likely benign | Familial hypercholesterolemia | 2017-11-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000776111 | SCV000752432 | likely benign | Familial hypercholesterolemia | 2025-01-30 | criteria provided, single submitter | clinical testing | |
| Fundacion Hipercolesterolemia Familiar | RCV000210234 | SCV000607422 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
| U4M - |
RCV000210234 | SCV000583635 | likely benign | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | ACMG Guidelines: Pathogenic (ii) |
| Molecular Genetics Laboratory, |
RCV000210234 | SCV000540896 | benign | Hypercholesterolemia, familial, 1 | 2017-03-16 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000455660 | SCV000539514 | uncertain significance | not specified | 2016-03-31 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 5 papers describe as VUS/nonpathogenic; ExAC: 0.1% (67/66532) European; ClinVar: 1 VUS |
| Centre de Génétique Moléculaire et Chromosomique, |
RCV000210234 | SCV000503105 | benign | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 4 , 2 compound heterozygous / Software predictions: Benign |
| Robarts Research Institute, |
RCV000210234 | SCV000484686 | likely benign | Hypercholesterolemia, familial, 1 | 2019-08-22 | criteria provided, single submitter | clinical testing | |
| LDLR- |
RCV000210234 | SCV000294487 | benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Cardiovascular Biomarker Research Laboratory, |
RCV000210234 | SCV000266309 | likely benign | Hypercholesterolemia, familial, 1 | 2015-08-31 | criteria provided, single submitter | research | MAF =<0.3% |
| CSER _CC_NCGL, |
RCV002051650 | SCV000190292 | uncertain significance | Hypercholesterolemia | 2014-06-01 | criteria provided, single submitter | research | Low GERP score may suggest that this variant may belong in a lower pathogenicity class |
| Prevention |
RCV003905026 | SCV004725353 | likely benign | LDLR-related disorder | 2019-06-18 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000455660 | SCV001966630 | benign | not specified | no assertion criteria provided | clinical testing | ||
| Clinical Genetics, |
RCV000455660 | SCV001922567 | benign | not specified | no assertion criteria provided | clinical testing | ||
| Diagnostic Laboratory, |
RCV000210234 | SCV000733812 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | clinical testing | ||
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000210234 | SCV000606027 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
| SNPedia | RCV000058916 | SCV000090437 | not provided | not provided | no assertion provided | not provided |