Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759006 | SCV000888015 | likely pathogenic | not provided | 2018-05-25 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000021916 | SCV000961511 | likely pathogenic | Biotinidase deficiency | 2018-07-19 | criteria provided, single submitter | clinical testing | This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with profound biotinidase deficiency (PMID: 9396567). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 24997). 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. The observation of one or more missense substitutions at this codon (p.Glu112Gln, p.Glu112Lys) in affected individuals suggests that this may be a clinically significant residue (PMID: 9396567, 14707518). 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 is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 112 of the BTD protein (p.Glu112Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000021916 | SCV005394661 | likely pathogenic | Biotinidase deficiency | 2024-09-25 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.274G>C (p.Glu92Gln) results in a conservative amino acid change located in the carbon-nitrogen hydrolase domain of the encoded protein sequence. This amino acid position has also been reported to be part of the catalytic triad active site (e.g.,Pindolia_2010 ). Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250318 control chromosomes. c.274G>C has been reported in the literature in two compound heterozygous siblings affected with Biotinidase Deficiency (e.g, Pomponio_1997, Norrgard_1999). These data indicate that the variant may be associated with disease. Additionally, serum from a patient compound heterozygous with a null variant, showed that this variant resulted in protein with no detectable hydrolase or transferase activity (e.g, Pomponio_1997). The following publications have been ascertained in the context of this evaluation (PMID: 10400129, 20556795, 9396567). ClinVar contains an entry for this variant (Variation ID: 24997). Based on the evidence outlined above, the variant was classified as likely pathogenic. |