Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000238476 | SCV000294469 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Labcorp Genetics |
RCV001854882 | SCV002254617 | uncertain significance | Familial hypercholesterolemia | 2021-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 36 of the LDLR protein (p.Asp36Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant familial hypercholesterolemia (PMID: 11810272, 20506408, Invitae). This variant is also known as D15E. ClinVar contains an entry for this variant (Variation ID: 251022). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002446471 | SCV002736613 | uncertain significance | Cardiovascular phenotype | 2022-08-18 | criteria provided, single submitter | clinical testing | The p.D36E variant (also known as c.108C>A), located in coding exon 2 of the LDLR gene, results from a C to A substitution at nucleotide position 108. The aspartic acid at codon 36 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration, which is also known as p.D15E, has been reported in a familial hypercholesterolemia (FH) cohort (Fouchier SW et al. Hum Genet, 2001 Dec;109:602-15). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238476 | SCV000606016 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |