Submissions for variant NM_001370658.1(BTD):c.249+1G>T

gnomAD frequency: 0.00001  dbSNP: rs373249212

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409760	SCV000486353	likely pathogenic	Biotinidase deficiency	2016-05-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000409760	SCV004476370	likely pathogenic	Biotinidase deficiency	2023-06-04	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370921). This variant has not been reported in the literature in individuals affected with BTD-related conditions. This variant is present in population databases (rs373249212, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 2 of the BTD gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BTD are known to be pathogenic (PMID: 20083419).