Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029290 | SCV000051936 | likely pathogenic | Adrenoleukodystrophy | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
Ambry Genetics | RCV000721083 | SCV000851969 | pathogenic | History of neurodevelopmental disorder | 2013-06-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000029290 | SCV000948152 | pathogenic | Adrenoleukodystrophy | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 280 of the ABCD1 protein (p.Arg280Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 11748843, 15811009; Invitae; https//adrenoleukodystrophy.info/mutations-and-variants-in-abcd1). ClinVar contains an entry for this variant (Variation ID: 35643). 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.Arg280 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in individuals with ABCD1-related conditions (PMID: 11798073), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Johns Hopkins Genomics, |
RCV000029290 | SCV000996044 | pathogenic | Adrenoleukodystrophy | 2019-05-08 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001781320 | SCV001474333 | likely pathogenic | not provided | 2020-06-18 | criteria provided, single submitter | clinical testing | The ABCD1 c.838C>T; p.Arg280Cys variant (rs193922098) is reported in several individuals with X-linked adrenoleukodystrophy and increased very-long-chain fatty acids (see link to ABCD1 variant database, Coll 2005, Isaacs 2014). The variant is reported as pathogenic or likely pathogenic by several sources in the ClinVar database (Variation ID: 35643) and is reported in the general population in 2 out of 128,935 alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 280 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. References: Link to ABCD1 database: https://adrenoleukodystrophy.info/mutations-and-variants-in-abcd1 Coll MJ et al. X-linked Adrenoleukodystrophy in Spain. Identification of 26 Novel Mutations in the ABCD1 Gene in 80 Patients. Improvement of Genetic Counseling in 162 Relative Females. Clin Genet. 2005 May;67(5):418-24. Isaacs D et al. Adult-onset Adrenoleukodystrophy Presenting After Chemotherapy: No Black and White Matter. Neurol Clin Pract. 2014 Apr;4(2):168-170. |
Revvity Omics, |
RCV001781320 | SCV002023955 | likely pathogenic | not provided | 2022-04-25 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000029290 | SCV002045815 | pathogenic | Adrenoleukodystrophy | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000029290 | SCV002811710 | pathogenic | Adrenoleukodystrophy | 2022-03-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001781320 | SCV004028109 | likely pathogenic | not provided | 2023-08-16 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29443243, 11748843, 33920672, 35466195, 35076462, 36076658, 15811009) |
Prevention |
RCV003407363 | SCV004113275 | pathogenic | ABCD1-related disorder | 2023-06-06 | criteria provided, single submitter | clinical testing | The ABCD1 c.838C>T variant is predicted to result in the amino acid substitution p.Arg280Cys. This variant has been reported in multiple unrelated individuals with adrenoleukodystrophy (Kemp et al. 2001. PubMed ID: 11748843; Coll et al. 2005. PubMed ID: 15811009; Isaacs et al. 2014. PubMed ID: 29443243). This variant is reported in 0.011% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-152991559-C-T). This variant is interpreted as pathogenic. |
Baylor Genetics | RCV000029290 | SCV005049415 | pathogenic | Adrenoleukodystrophy | 2024-03-27 | criteria provided, single submitter | clinical testing |