Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000238382 | SCV000294709 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Color Diagnostics, |
RCV001526129 | SCV001736422 | uncertain significance | Familial hypercholesterolemia | 2023-02-01 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Val124Ala in the mature protein) replaces valine with alanine at codon 145 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in six individuals showing LDL-C levels not significantly higher than control individuals (Hartgers 2020 dissertation, Univ. Amsterdam). This variant has been identified in 5/282590 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is no indication this variant causes disease, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| All of Us Research Program, |
RCV000238382 | SCV004820170 | uncertain significance | Hypercholesterolemia, familial, 1 | 2024-09-23 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with alanine at codon 145 of the LDLR protein. This variant is also known as p.Val124Ala in the mature protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 16250003) as well as in six individuals showing LDL-C levels not significantly higher than control individuals (Hartgers 2020 dissertation, Univ. Amsterdam). This variant has been identified in 5/282590 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is no indication this variant causes disease, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004992113 | SCV005612289 | uncertain significance | Cardiovascular phenotype | 2024-10-16 | criteria provided, single submitter | clinical testing | The p.V145A variant (also known as c.434T>C), located in coding exon 4 of the LDLR gene, results from a T to C substitution at nucleotide position 434. The valine at codon 145 is replaced by alanine, an amino acid with similar properties. This variant has been reported in a familial hypercholesterolemia (FH) cohort, but clinical details were limited (Fouchier SW et al. Hum Mutat, 2005 Dec;26:550-6). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238382 | SCV000606119 | benign | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |