Submissions for variant NM_000033.4(ABCD1):c.1568T>C (p.Leu523Pro)

dbSNP: rs2091762647

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001218702	SCV001390598	pathogenic	Adrenoleukodystrophy	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 523 of the ABCD1 protein (p.Leu523Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of adrenoleukodystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 947594). 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. This variant disrupts the p.Leu523 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21700483). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics, Johns Hopkins University	RCV001218702	SCV001425400	likely pathogenic	Adrenoleukodystrophy	2020-04-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001218702	SCV002045768	uncertain significance	Adrenoleukodystrophy	2021-11-07	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001218702	SCV002084646	uncertain significance	Adrenoleukodystrophy	2020-04-01	no assertion criteria provided	clinical testing