ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1192T>C (p.Cys398Arg) (rs397514408)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Research and Development, ARUP Laboratories RCV000021994 SCV000042664 pathogenic Biotinidase deficiency 2017-02-17 criteria provided, single submitter clinical testing Enzyme activity @ 1.9 U/L w/no paired control. Seen with c.13330G>C,p.D444H-het and c.1413T>C,p.C471C.
Counsyl RCV000021994 SCV000800681 uncertain significance Biotinidase deficiency 2018-03-27 criteria provided, single submitter clinical testing
Invitae RCV000021994 SCV000938428 pathogenic Biotinidase deficiency 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 418 of the BTD protein (p.Cys418Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another BTD variant in individuals affected with biotinidase deficiency (PMID: 26810761, 27329734, Invitae). ClinVar contains an entry for this variant (Variation ID: 25069). 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.Cys418Arg and p.Cys418Ser) in affected individuals suggests that this may be a clinically significant residue (PMID: 14707518). For these reasons, this variant has been classified as Pathogenic.

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