Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Preventiongenetics, |
RCV000223787 | SCV000316576 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Cardiovascular Research Group, |
RCV000256353 | SCV000323028 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | MAF = 9% in 100 subjects with average plasma cholesterol |
Color Diagnostics, |
RCV000256353 | SCV000690984 | benign | Hypercholesterolemia, familial, 1 | 2017-07-07 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000625171 | SCV000743995 | benign | Hypercholesterolemia, autosomal dominant, 3 | 2016-04-26 | criteria provided, single submitter | clinical testing | |
Iberoamerican FH Network | RCV000256353 | SCV000748065 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Color Diagnostics, |
RCV000776608 | SCV000912224 | benign | Familial hypercholesterolemia | 2018-05-21 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000845341 | SCV000987387 | likely benign | not provided | criteria provided, single submitter | clinical testing | ||
Invitae | RCV000625171 | SCV001725597 | benign | Hypercholesterolemia, autosomal dominant, 3 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000845341 | SCV001894657 | benign | not provided | 2016-11-15 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 29562810, 30782561, 26687699, 25239117, 23743349, 16619215, 23663650, 20006333) |
ARUP Laboratories, |
RCV000845341 | SCV002048042 | benign | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002354623 | SCV002655980 | benign | Cardiovascular phenotype | 2015-12-14 | 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000845341 | SCV004222383 | benign | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000223787 | SCV000280405 | benign | not specified | 2013-01-30 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. c.63_65dupGCT in PCKS9 (aka c.61_63dupCTG, c.43_44insCTG, L21dup, L10, p.L15_16insL). This is an in-frame duplication of three nucleotides which results in insertion of a leucine in a 9-leucine track. The variant has been seen in at least 8 unrelated cases of familial hypercholesterolemia however it has also been observed at appreciable frequencies in individuals from the general population with normal cholesterol. Noguchi et al (2010) reported that 8 of 55 familial hypercholesterolemia patients without LDLR variants were heterozygous for this variant. No segregation or control data was provided. In total the variant has been seen in the homozygous state in 11 of 822 individuals and in the heterozygous state in 204 of 822 individuals from published reports and publicly available population datasets. The variant is listed in dbSNP as rs35574083 without minor allele frequency data. Another dbSNP entry, rs45454392, also represents a leucine insertion in the same track of leucine repeats, denoted c.44_45insGCT (p.Leu15delinsLeuLeu). These variants are likely synonymous as it would be impossible to know exactly where the insertion occurred in the repeat track and different groups would choose to number at different points in the track, but with both insertions leading to an additional leucine. The latter dbSNP entry includes minor allele frequency data from general populations samples in the Coriell repository with 2/24 African Americans being homozygotes for the insertion and 9/24 African American and 4/23 European individuals noted as heterozygotes. Chen et al (2005) reported allele frequencies for the L9, L10, and L11 variants in the Lipoprotein Coronary Atherosclerosis Study population (LCAS). The sample consistent of 372 35-75yo individuals with LDL-C levels of 115 to 190 mg/dL despite diet and one more coronary lesions of 30-75% stenosis.. Given this selection criteria this cannot be considered a general population sample, however their LDL levels indicate they likely did not have familial hypercholesterolemia. 90/372 individuals studied were heterozygotes for the L10 variant. Yue et al (2006) reported that in a general population sample with normal cholesterol phenotypes 101/403 individuals were heterozygoes for the L10 allele and 9/403 were homozygous. Unfortunately the NHLBI Exome Sequencing Project dataset only reports single nucleotide variation so no data is provided on this variant. Yue et al (2006) found that the variant is associated with lower LDL-C in a Caucasian sample with normal cholesterol. Individuals who had one 9 repeat copy and one 10 repeat copy (i.e. heterozygotes for this variant) had LDL-C that was 10-15 mg/dL lower. They found the 10 repeat variant was an independent predictor of LDL-C. Pisciotta et al (2011) compared total cholesterol LDL-C levels in familial hypercholesterolemia patients who were heterozygous for the 10 repeat variant with those who were homozygous for the wildtype 9 repeat variant and found no differences. However, in the subgroup of individuals treated with statins, the reduction in both total cholesterol and LDL-C was greater in heterozygotes for L10 than in wildtype homozygotes. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000256353 | SCV000606673 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000223787 | SCV001740953 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000223787 | SCV001926190 | benign | not specified | no assertion criteria provided | clinical testing | ||
Cohesion Phenomics | RCV000776608 | SCV003836771 | benign | Familial hypercholesterolemia | 2023-02-09 | no assertion criteria provided | clinical testing |