ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1817C>T (p.Ser606Leu) (rs128624225)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000517966 SCV000232463 pathogenic not provided 2014-08-07 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000517966 SCV000612232 pathogenic not provided 2017-07-24 criteria provided, single submitter clinical testing
Invitae RCV000180094 SCV000629995 pathogenic Adrenoleukodystrophy 2018-02-13 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 606 of the ABCD1 protein (p.Ser606Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (rs128624225, ExAC no frequency). This variant has been reported in several individuals affected with various forms of X-linked adrenoleukodystrophy including Addison's disease and adrenomyeloneuropathy (PMID: 7581394, 8040304, 10190819, 12624723, 14767898, 15811009, 22479560). ClinVar contains an entry for this variant (Variation ID: 11310). Experimental studies have shown that this missense change results in decreased ATP binding affinity and ABCD1 protein degradation in vitro (PMID: 11248239, 12530690, 17542813). For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000180094 SCV000998462 pathogenic Adrenoleukodystrophy 2019-07-05 criteria provided, single submitter clinical testing This previously reported variant (rs128624225) has been identified in multiple patients with clinical and biochemical findings consistent with ABCD1 related disease. Four submitters in ClinVar classify this variant as pathogenic. Additionally, functional analysis supports the deleterious effect of this this variant on protein function. This variant is considered pathogenic.
OMIM RCV000012062 SCV000032296 pathogenic Addison's disease 1994-08-01 no assertion criteria provided literature only

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