Submissions for variant NM_001370658.1(BTD):c.1568A>T (p.Asp523Val)

gnomAD frequency: 0.00003  dbSNP: rs1050035768

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003230963	SCV003929214	uncertain significance	not specified	2023-04-13	criteria provided, single submitter	clinical testing	Variant summary: BTD c.1568A>T (p.Asp523Val) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.2e-06 in 236628 control chromosomes (gnomAD). c.1568A>T has been reported in the literature in at least one compound heterozygous individual affected with Biotinidase Deficiency (Procter_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, different substitutions at the same codon have been classified as pathogenic/likely pathogenic within ClinVar, suggesting this amino acid residue may be important for normal protein function (e.g. c.1568A>G [p.Asp523Gly], c.1569C>A [p.Asp523Glu]). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics	RCV003475551	SCV004211470	likely pathogenic	Biotinidase deficiency	2023-03-30	criteria provided, single submitter	clinical testing