Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534849 | SCV000629990 | pathogenic | Adrenoleukodystrophy | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 509 of the ABCD1 protein (p.Asn509Ser). This variant is present in population databases (rs782158792, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of adrenoleukodystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 458633). 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 ABCD1 protein function with a positive predictive value of 95%. This variant disrupts the p.Asn509 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in individuals with ABCD1-related conditions (PMID: 14767898, 16415970), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002395316 | SCV002709654 | uncertain significance | Inborn genetic diseases | 2017-11-10 | criteria provided, single submitter | clinical testing | The p.N509S variant (also known as c.1526A>G), located in coding exon 6 of the ABCD1 gene, results from an A to G substitution at nucleotide position 1526. The asparagine at codon 509 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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. |
Revvity Omics, |
RCV003488661 | SCV004238403 | likely pathogenic | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000534849 | SCV002084643 | uncertain significance | Adrenoleukodystrophy | 2020-10-07 | no assertion criteria provided | clinical testing |