Submissions for variant NM_000033.4(ABCD1):c.529C>T (p.Gln177Ter)

dbSNP: rs1057516052

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000408645	SCV000484487	pathogenic	not provided	2016-06-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001290674	SCV001478806	pathogenic	Adrenoleukodystrophy	2021-01-25	criteria provided, single submitter	clinical testing	Variant summary: ABCD1 c.529C>T (p.Gln177X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 182774 control chromosomes (gnomAD). c.529C>T has been reported in the literature in individuals affected with Adrenoleukodystrophy (e.g. Lachtenmacher_2000, Asheuer_2005, Coll_2005, Lan_2011). These data indicate that the variant is likely to be associated with disease. Experimental evidence indicates that patient fibroblasts with the variant fail to express detectable levels of ALDP protein (e.g. Coll_2005). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab	RCV001290674	SCV002045808	pathogenic	Adrenoleukodystrophy	2021-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001290674	SCV002240246	pathogenic	Adrenoleukodystrophy	2021-05-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with ABCD1-related conditions (PMID: 10737980, 24480483). ClinVar contains an entry for this variant (Variation ID: 369726). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln177*) 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).
Baylor Genetics	RCV001290674	SCV003835290	pathogenic	Adrenoleukodystrophy	2021-03-08	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001290674	SCV005374407	pathogenic	Adrenoleukodystrophy	2024-09-22	criteria provided, single submitter	clinical testing