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

gnomAD frequency: 0.00020  dbSNP: rs201023772

Total submissions: 6

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	2024-08-01	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 compound heterozygous genotype with partial biotinidase deficiency or a presumably compound heterozygous genotype in settings of newborn screening workup among individuals affected with Partial Biotinidase Deficiency (e.g. Ohlsson_2010, Jay_2015, Sharma_2024). These report(s) do not provide unequivocal conclusions about association of the variant with Biotinidase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25144890, 20224900, 38299772). ClinVar contains an entry for this variant (Variation ID: 25062). 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