ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1552C>A (p.Arg518Ser) (rs80338686)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409281 SCV000486616 likely pathogenic Biotinidase deficiency 2016-07-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623390 SCV000742654 pathogenic Inborn genetic diseases 2017-06-16 criteria provided, single submitter clinical testing
Invitae RCV000409281 SCV000754945 pathogenic Biotinidase deficiency 2017-09-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 538 of the BTD protein (p.Arg538Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs80338686, ExAC 0.02%). This variant has been reported as homozygous in two individuals affected with biotinidase deficiency (PMID: 22698809, Invitae). It has also been found in the heterozygous state in an independent individual with biotinidase deficiency (PMID: 22698809). ClinVar contains an entry for this variant (Variation ID: 203642). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg538Cys) has been determined to be pathogenic (PMID: 9099842, 26810761, 27207447). This suggests that the arginine 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.
Research and Development, ARUP Laboratories RCV000409281 SCV000845836 uncertain significance Biotinidase deficiency 2017-02-17 criteria provided, single submitter clinical testing Seen multiple times, most often with c.13330G>C,p.D444H. Enzyme activities range from <0.4 U/L to 2.2 U/L.

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