Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000238555 | SCV000295503 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000238555 | SCV001653641 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003298317 | SCV004000128 | uncertain significance | Cardiovascular phenotype | 2023-04-17 | criteria provided, single submitter | clinical testing | The p.D525V variant (also known as c.1574A>T), located in coding exon 10 of the LDLR gene, results from an A to T substitution at nucleotide position 1574. The aspartic acid at codon 525 is replaced by valine, an amino acid with highly dissimilar properties. This alteration (also noted as p.D504V) has been reported in association with familial hypercholesterolemia (FH) (Bunn CF et al. Hum Mutat, 2002 Mar;19:311; Humphries SE et al. J Mol Med (Berl), 2006 Mar;84:203-14; Di Taranto MD et al. Clin Genet, 2021 Nov;100:529-541). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003581628 | SCV004298363 | likely pathogenic | Familial hypercholesterolemia | 2023-03-07 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 expected to disrupt LDLR protein function. ClinVar contains an entry for this variant (Variation ID: 251902). This variant is also known as c.1573A>T (p.D504V). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 15556094, 16389549). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 525 of the LDLR protein (p.Asp525Val). |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238555 | SCV000606456 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |