Submissions for variant NM_001370658.1(BTD):c.187_195del (p.Leu63_Leu65del)

dbSNP: rs397514346

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001929892	SCV002130589	uncertain significance	Biotinidase deficiency	2021-02-22	criteria provided, single submitter	clinical testing	This variant, c.247_255del, results in the deletion of 3 amino acid(s) of the BTD protein (p.Leu83_Leu85del), but otherwise preserves the integrity of the reading frame. 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. This variant disrupts a region of the protein in which other variant(s) (p.Leu83Ser) have been observed in individuals with BTD-related conditions (PMID: 20224900). This suggests that this may be a clinically significant region of the BTD protein. This variant has been observed in individual(s) with biotinidase deficiency (PMID: 9396567). ClinVar contains an entry for this variant (Variation ID: 587750). This variant is not present in population databases (ExAC no frequency).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003155434	SCV003844449	uncertain significance	not specified	2023-02-08	criteria provided, single submitter	clinical testing	Variant summary: BTD c.187_195delTTGGAGCTC (p.Leu63_Leu65del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant was absent in 251408 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.187_195delTTGGAGCTC has been reported in the literature in at least one individual affected with Biotinidase Deficiency (e.g., Pomponio_1997, Norrgard_1999). 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.