Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237637 | SCV000296025 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Laboratory for Molecular Medicine, |
RCV000456063 | SCV000539512 | uncertain significance | not specified | 2016-03-28 | 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: 1 paper in HGMD; Absent from ExAC with good coverage |
| Mayo Clinic Laboratories, |
RCV001509016 | SCV001715501 | uncertain significance | not provided | 2019-09-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002429178 | SCV002742365 | uncertain significance | Cardiovascular phenotype | 2022-04-20 | criteria provided, single submitter | clinical testing | The p.V836I variant (also known as c.2506G>A), located in coding exon 17 of the LDLR gene, results from a G to A substitution at nucleotide position 2506. The valine at codon 836 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Fouchier SW et al. Hum. Mutat., 2005 Dec;26:550-6; Leigh SE et al. Ann. Hum. Genet., 2008 Jul;72:485-98). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001509016 | SCV003927449 | uncertain significance | not provided | 2023-05-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as p.V815I; This variant is associated with the following publications: (PMID: 18325082, 22079632, 34426522, 16250003) |
| Color Diagnostics, |
RCV003581646 | SCV004359074 | uncertain significance | Familial hypercholesterolemia | 2023-07-24 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Val815Ile in the mature protein) replaces valine with isoleucine at codon 836 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with familial hypercholesterolemia (PMID: 16250003, 18325082). This variant has been identified in 1/251448 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237637 | SCV000606664 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |