Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000405919 | SCV000335421 | uncertain significance | not provided | 2015-10-12 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000021987 | SCV000800620 | uncertain significance | Biotinidase deficiency | 2017-11-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000021987 | SCV000813112 | uncertain significance | Biotinidase deficiency | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 402 of the BTD protein (p.Asn402Ser). This variant is present in population databases (rs201023772, gnomAD 0.03%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 20224900, 25144890). ClinVar contains an entry for this variant (Variation ID: 25062). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002281714 | SCV002571928 | uncertain significance | not specified | 2022-08-10 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.1145A>G (p.Asn382Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 251392 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BTD causing Biotinidase Deficiency (0.00017 vs 0.0046), allowing no conclusion about variant significance. c.1145A>G has been reported in the literature as a presumably compound heterozygous genotype in settings of newborn screening workup among individuals affected with Partial Biotinidase Deficiency (example, Ohlsson_2010, Jay_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Biotinidase Deficiency. To our knowledge, no variant specific 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 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Fulgent Genetics, |
RCV000021987 | SCV002778295 | uncertain significance | Biotinidase deficiency | 2021-07-20 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000021987 | SCV002081573 | uncertain significance | Biotinidase deficiency | 2020-02-11 | no assertion criteria provided | clinical testing |