Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CSER _CC_NCGL, |
RCV000148578 | SCV000190292 | uncertain significance | Hypercholesterolaemia | 2014-06-01 | criteria provided, single submitter | research | Low GERP score may suggest that this variant may belong in a lower pathogenicity class |
Cardiovascular Biomarker Research Laboratory, |
RCV000210234 | SCV000266309 | likely benign | Familial hypercholesterolemia 1 | 2015-08-31 | criteria provided, single submitter | research | MAF =<0.3% |
LDLR- |
RCV000210234 | SCV000294487 | benign | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Robarts Research Institute, |
RCV000210234 | SCV000484686 | likely benign | Familial hypercholesterolemia 1 | 2019-08-22 | criteria provided, single submitter | clinical testing | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000210234 | SCV000503105 | benign | Familial hypercholesterolemia 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 |
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 |
Molecular Genetics Laboratory, |
RCV000210234 | SCV000540896 | benign | Familial hypercholesterolemia 1 | 2017-03-16 | criteria provided, single submitter | clinical testing | |
U4M - |
RCV000210234 | SCV000583635 | likely benign | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | ACMG Guidelines: Pathogenic (ii) |
Fundacion Hipercolesterolemia Familiar | RCV000210234 | SCV000607422 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Invitae | RCV000776111 | SCV000752432 | likely benign | Familial hypercholesterolemia | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Color | RCV000776111 | SCV000910984 | likely benign | Familial hypercholesterolemia | 2017-11-23 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000455660 | SCV000919594 | likely benign | not specified | 2020-09-16 | 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 Low-density lipoprotein (LDL) receptor class A repeat region 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 0.00051 in 294358 control chromosomes (gnomAD and publications). This frequency is not significantly higher than expected for a pathogenic variant in LDLR causing Familial Hypercholesterolemia (0.00051 vs 0.0013), allowing no conclusion about variant significance. The variant, c.148G>T, has been reported in the literature in individuals affected with Familial Hypercholesterolemia but also 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). These reports do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. In one family, the variant was found to not segregate with disease (Jensen_1994). Co-occurrences with other pathogenic variants have been reported (LDLR c.12G>A, p.Trp4X; LDLR c.1033C>T, p.Gln345X), providing supporting evidence for a benign role (Tejedor_2010, internal database). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 12 ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (3x), likely benign (6x) and benign (3x). Based on the evidence outlined above, the variant was classified as likely benign. |
Illumina Clinical Services Laboratory, |
RCV000210234 | SCV001281756 | likely benign | Familial hypercholesterolemia 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. |
Institute of Human Genetics, |
RCV000210234 | SCV001429403 | uncertain significance | Familial hypercholesterolemia 1 | 2019-02-04 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000058916 | SCV001433284 | uncertain significance | not provided | 2020-02-17 | criteria provided, single submitter | clinical testing | |
SNPedia | RCV000058916 | SCV000090437 | not provided | not provided | no assertion provided | not provided | ||
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000210234 | SCV000606027 | benign | Familial hypercholesterolemia 1 | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000210234 | SCV000733812 | benign | Familial hypercholesterolemia 1 | no assertion criteria provided | clinical testing |