ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1207T>C (p.Cys403Arg) (rs397514412)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000021998 SCV000800683 uncertain significance Biotinidase deficiency 2018-03-26 criteria provided, single submitter clinical testing
Invitae RCV000021998 SCV000942909 likely pathogenic Biotinidase deficiency 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 423 of the BTD protein (p.Cys423Arg). 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: 9396567, 27657684). ClinVar contains an entry for this variant (Variation ID: 25073). 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. This variant disrupts the p.Cys423 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 11313766), which suggests that this may be a clinically significant amino acid residue. 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 RCV000021998 SCV000042668 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only

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