ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1569C>A (p.Asp523Glu) (rs146136265)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000022028 SCV000798766 likely pathogenic Biotinidase deficiency 2018-03-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078071 SCV000109909 pathogenic not provided 2018-01-03 criteria provided, single submitter clinical testing
Invitae RCV000022028 SCV000630332 pathogenic Biotinidase deficiency 2017-07-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 543 of the BTD protein (p.Asp543Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs146136265, ExAC 0.1%). This variant has been reported as homozygous in an individual affected with partial biotinidase deficiency (PMID: 25967232). It has also been reported  in combination with other BTD variants in individuals affected with partial and profound biotinidase deficiency (PMID: 28498829, 25174816). ClinVar contains an entry for this variant (Variation ID: 25103). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In addition, two different missense substitutions at this codon (p.Asp543Val, p.Asp543His) have been reported as pathogenic (PMID: 26810761). This suggests that the aspartic acid residue is critical for BTD protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000078071 SCV000888013 pathogenic not provided 2018-08-24 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV000022028 SCV000042703 pathogenic Biotinidase deficiency 2017-02-17 criteria provided, single submitter clinical testing Enzyme activity @ 2.4 U/L with paired control in normal range. Seen with c.1330G>C,p.D444H.

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