ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1535C>T (p.Thr512Met) (rs104893688)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000001974 SCV000220463 pathogenic Biotinidase deficiency 2014-06-29 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185809 SCV000330913 pathogenic not provided 2015-08-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000001974 SCV000894301 pathogenic Biotinidase deficiency 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000185809 SCV000238753 pathogenic not provided 2018-11-02 criteria provided, single submitter clinical testing The T532M missense variant in the BTD gene has been reported previously in association with profound biotinidase deficiency (Pomponio et al., 2000).
Invitae RCV000001974 SCV000630330 pathogenic Biotinidase deficiency 2017-10-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 532 of the BTD protein (p.Thr532Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs104893688, ExAC 0.009%). This variant has been reported to be a common cause of biotinidase deficiency in Mediterranean populations, although it has also been described in affected individuals from other ethnic backgrounds (PMID: 9654207, 10801053, 21752405, 22698809, 10400129, 22011816, 27657684). ClinVar contains an entry for this variant (Variation ID: 1897). 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. Although these predictions have not been confirmed by direct functional studies, homozygous individuals show 10-40% of serum biotinidase activity (PMID: 10400129, 10801053, 25174816). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001974 SCV000022132 pathogenic Biotinidase deficiency 2000-03-01 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000185809 SCV000888012 pathogenic not provided 2015-09-11 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV000001974 SCV000042696 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only

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