Submissions for variant NM_000033.4(ABCD1):c.1675T>C (p.Tyr559His)

dbSNP: rs2091764510

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001223848	SCV001396015	likely pathogenic	Adrenoleukodystrophy	2023-03-10	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 951851). 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. 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. This missense change has been observed in individuals with adrenoleukodystrophy (PMID: 9242200). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 559 of the ABCD1 protein (p.Tyr559His). This variant is not present in population databases (gnomAD no frequency).
Natera, Inc.	RCV001223848	SCV002084648	uncertain significance	Adrenoleukodystrophy	2021-04-20	no assertion criteria provided	clinical testing