ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.829G>A (p.Gly277Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000807408 SCV000947456 likely pathogenic Adrenoleukodystrophy 2018-10-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 277 of the ABCD1 protein (p.Gly277Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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 been observed in several individuals affected with X-linked adrenoleukodystrophy (X-ALD) (PMID: 8566952, 15811009, 20661612). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Gly277 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 7581394), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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