Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000021942 | SCV000800562 | uncertain significance | Biotinidase deficiency | 2017-07-17 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000727575 | SCV000854816 | likely pathogenic | not provided | 2018-01-03 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000021942 | SCV001391009 | pathogenic | Biotinidase deficiency | 2022-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 195 of the BTD protein (p.Asn195Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 9396567, 11865279). ClinVar contains an entry for this variant (Variation ID: 25021). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Asn195 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 17185019), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298448 | SCV002598711 | uncertain significance | not specified | 2022-09-27 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.523A>G (p.Asn175Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251454 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.523A>G has been reported in the literature in an individual affected with Biotinidase Deficiency (example: Pomponio_1997). This information is insufficient to allow any conclusion about the variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=1) and pathogenic/likely pathogenic (n=3). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV000021942 | SCV002081555 | pathogenic | Biotinidase deficiency | 2021-04-20 | no assertion criteria provided | clinical testing |