Submissions for variant NM_001370658.1(BTD):c.862A>C (p.Met288Leu)

dbSNP: rs757604137

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000665673	SCV000789832	uncertain significance	Biotinidase deficiency	2017-02-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001779041	SCV002015079	uncertain significance	not specified	2021-10-27	criteria provided, single submitter	clinical testing	Variant summary: BTD c.862A>C (p.Met288Leu) results in a conservative amino acid change located in the Carbon-nitrogen hydrolase domain (IPR003010) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251386 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.862A>C has been reported in the literature in a compound heterozygous individual through newborn screening for inborn errors of metabolism (Al-Jasmi_2016). This report does 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. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.