ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1350dup (p.Cys451fs) (rs886041559)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000296640 SCV000330236 pathogenic not provided 2016-02-13 criteria provided, single submitter clinical testing The c.1410dupC variant in the BTD gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1410dupC variant causes a frameshift starting with codon Cysteine 471, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Cys471LeufsX13. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1410dupC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1410dupC as a pathogenic variant.
Invitae RCV000411318 SCV001198039 pathogenic Biotinidase deficiency 2019-12-13 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BTD gene (p.Cys471Leufs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acids of the BTD protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BTD-related conditions. ClinVar contains an entry for this variant (Variation ID: 280333). This variant disrupts the C-terminus of the BTD protein. Other variant(s) that disrupt this region (p.Leu498Phefs*13) have been determined to be pathogenic (PMID: 17382128, 29359854, 19728141, 29359854). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000411318 SCV000486858 likely pathogenic Biotinidase deficiency 2016-08-24 no assertion criteria provided clinical testing

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