ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1193G>C (p.Cys398Ser) (rs397514410)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000021996 SCV001575614 likely pathogenic Biotinidase deficiency 2020-01-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 418 of the BTD protein (p.Cys418Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is present in population databases (rs397514410, ExAC 0.006%). This variant has been observed in individual(s) with biotinidase deficiency (PMID: 14707518). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 25071). 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.Cys418 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26810761, 27329734). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV000021996 SCV000042666 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only

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