Submissions for variant NM_000033.4(ABCD1):c.1359del (p.Gly454fs)

dbSNP: rs1603234574

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008779	SCV001168570	pathogenic	not provided	2019-05-03	criteria provided, single submitter	clinical testing	The c.1359delT variant has been reported previously in association in a male patient with X-linked adrenoleukodystrophy (X-ALD) with no detectable expression of adrenoleukodystrophy protein in fibroblasts (Coll et al. 2005). The c.1359delT variant is not observed in large population cohorts (Lek et al., 2016). The deletion causes a frameshift starting with codon Glycine 454, changes this amino acid to a Valine residue and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Gly454ValfsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001008779	SCV001473538	pathogenic	not provided	2019-09-27	criteria provided, single submitter	clinical testing	The ABCD1 c.1359delT; p.Gly454fs variant is reported in the literature in an individual with X-linked adrenoleukodystrophy (Coll 2005). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES 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.
Genome-Nilou Lab	RCV001800915	SCV002045825	pathogenic	Adrenoleukodystrophy	2021-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001800915	SCV002238682	pathogenic	Adrenoleukodystrophy	2021-12-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly454Valfs*8) in the ABCD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 15811009). ClinVar contains an entry for this variant (Variation ID: 817611). For these reasons, this variant has been classified as Pathogenic.