Submissions for variant NM_183050.4(BCKDHB):c.1065del (p.Pro356fs)

dbSNP: rs869312129

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV000209501	SCV000240040	pathogenic	Maple syrup urine disease	2011-01-01	criteria provided, single submitter	research
Counsyl	RCV000209501	SCV000795582	pathogenic	Maple syrup urine disease	2017-11-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000209501	SCV001209222	pathogenic	Maple syrup urine disease	2024-02-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro356Leufs*34) in the BCKDHB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the BCKDHB protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with maple syrup urine disease (PMID: 22593002, 26257134). ClinVar contains an entry for this variant (Variation ID: 224059). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000209501	SCV001983713	pathogenic	Maple syrup urine disease	2021-09-26	criteria provided, single submitter	clinical testing	Variant summary: BCKDHB c.1065delT (p.Pro356LeufsX34) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251226 control chromosomes. c.1065delT has been reported in the literature in multiple individuals affected with Maple Syrup Urine Disease (example, Bashyam_2012, Gupta_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab	RCV000209501	SCV002033167	pathogenic	Maple syrup urine disease	2021-11-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000209501	SCV004215985	pathogenic	Maple syrup urine disease	2023-05-13	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001833174	SCV002079885	pathogenic	Maple syrup urine disease type 1B	2020-12-04	no assertion criteria provided	clinical testing