ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1825G>A (p.Glu609Lys) (rs150346282)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723952 SCV000202107 pathogenic not provided 2014-05-01 criteria provided, single submitter clinical testing
Invitae RCV000152721 SCV000629996 pathogenic Adrenoleukodystrophy 2018-05-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 609 of the ABCD1 protein (p.Glu609Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN), and adult cerebral adrenoleukodystrophy (PMID: 7825602, 20661612, 11748843, 21966424). ClinVar contains an entry for this variant (Variation ID: 166626). Immunofluorescence analysis of patient-derived fibroblasts bearing this missense change failed to detect adrenoleukodystrophy protein (ALDP), the protein product of ABCD1 gene (PMID: 21476988). A different missense substitution at this codon (p.Glu609Gly) has been determined to be pathogenic (PMID: 7825602, 21476988). This suggests that the glutamic acid residue is critical for ABCD1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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