Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001182968 | SCV001348605 | uncertain significance | Familial hypercholesterolemia | 2023-03-29 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Asp4Asn in the mature protein) replaces aspartic acid with asparagine at codon 25 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 not been reported in individuals affected with LDLR-related disorders in the literature. This variant has been identified in 5/281898 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. |
Ambry Genetics | RCV002379705 | SCV002671223 | uncertain significance | Cardiovascular phenotype | 2021-04-08 | criteria provided, single submitter | clinical testing | The p.D25N variant (also known as c.73G>A), located in coding exon 2 of the LDLR gene, results from a G to A substitution at nucleotide position 73. The aspartic acid at codon 25 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and aspargine is the reference amino acid in other 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. |
Fulgent Genetics, |
RCV002491531 | SCV002781440 | uncertain significance | Hypercholesterolemia, familial, 1 | 2021-07-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001182968 | SCV003299405 | uncertain significance | Familial hypercholesterolemia | 2022-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 25 of the LDLR protein (p.Asp25Asn). This variant is present in population databases (rs562712652, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 922750). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LDLR protein function. 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. |
Revvity Omics, |
RCV002491531 | SCV003816530 | uncertain significance | Hypercholesterolemia, familial, 1 | 2022-06-09 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV002491531 | SCV004820110 | uncertain significance | Hypercholesterolemia, familial, 1 | 2024-05-17 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Asp4Asn in the mature protein) replaces aspartic acid with asparagine at codon 25 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 not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 5/281898 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. |