ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.274G>C (p.Glu92Gln) (rs397514352)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759006 SCV000888015 likely pathogenic not provided 2018-05-25 criteria provided, single submitter clinical testing
Invitae RCV000021916 SCV000961511 likely pathogenic Biotinidase deficiency 2018-07-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 112 of the BTD protein (p.Glu112Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with profound biotinidase deficiency (PMID: 9396567). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 24997). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The observation of one or more missense substitutions at this codon (p.Glu112Gln, p.Glu112Lys) in affected individuals suggests that this may be a clinically significant residue (PMID: 9396567, 14707518). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Research and Development, ARUP Laboratories RCV000021916 SCV000042585 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only

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