ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.839G>C (p.Arg280Pro)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiogenetic Research Center,Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences RCV001090114 SCV001244678 likely pathogenic Adrenoleukodystrophy 2019-07-05 criteria provided, single submitter research
Invitae RCV001090114 SCV001503705 uncertain significance Adrenoleukodystrophy 2020-02-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 280 of the ABCD1 protein (p.Arg280Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with ABCD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). This variant disrupts the p.Arg280 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29443243, 15811009, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence, RCV001090114 SCV001244951 uncertain significance Adrenoleukodystrophy no assertion criteria provided clinical testing

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