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	2024-03-11	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. The following publication has been ascertained in the context of this evaluation (PMID: 26589311). ClinVar contains an entry for this variant (Variation ID: 550822). Based on the evidence outlined above, the variant was classified as uncertain significance.