Submissions for variant NM_000033.4(ABCD1):c.887A>G (p.Tyr296Cys)

dbSNP: rs797044610

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724285	SCV000224131	pathogenic	not provided	2014-09-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000173051	SCV000754726	pathogenic	Adrenoleukodystrophy	2024-11-12	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 296 of the ABCD1 protein (p.Tyr296Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 10190819, 11748843, 15800013, 16087056, 16415970, 21068741, 22479560, 25275259, 26454440; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 193033). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000173051	SCV001367718	pathogenic	Adrenoleukodystrophy	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PM5,PP2,PP3. This variant was detected in hemizygous state.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000173051	SCV001934308	likely pathogenic	Adrenoleukodystrophy	2020-11-10	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000724285	SCV002019429	pathogenic	not provided	2022-02-17	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000173051	SCV002045817	pathogenic	Adrenoleukodystrophy	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002372080	SCV002684532	likely pathogenic	Inborn genetic diseases	2017-11-30	criteria provided, single submitter	clinical testing	The p.Y296C variant (also known as c.887A>G), located in coding exon 1 of the ABCD1 gene, results from an A to G substitution at nucleotide position 887. The tyrosine at codon 296 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a few individuals with adrenoleukodystrophy (Takano H et al. Arch. Neurol., 1999 Mar;56:295-300; Kemp S et al. Hum. Mutat., 2001 Dec;18:499-515; Pan H et al. Pediatr. Neurol., 2005 Aug;33:114-20; Asheuer M et al. Hum. Mol. Genet., 2005 May;14:1293-303; Sutovský S et al. Neuro Endocrinol. Lett., 2014;35:411-6; Chu SS et al. World J Pediatr, 2015 Nov;11:366-73). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000724285	SCV004702246	pathogenic	not provided	2024-07-01	criteria provided, single submitter	clinical testing	ABCD1: PM1, PM2, PM5, PP1:Moderate, PS4:Moderate, PP3