ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1145A>G (p.Asn382Ser)

gnomAD frequency: 0.00020  dbSNP: rs201023772
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) 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 (formerly Invitae), Labcorp 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, LabCorp 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, Fulgent Genetics RCV000021987 SCV002778295 uncertain significance Biotinidase deficiency 2021-07-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV000021987 SCV002081573 uncertain significance Biotinidase deficiency 2020-02-11 no assertion criteria provided clinical testing

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