Submissions for variant NM_183050.4(BCKDHB):c.580C>T (p.Leu194Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pediatric/Medical Genetics, Ministry of Health, Qatif Central Hospital	RCV003149167	SCV003836803	pathogenic	Maple syrup urine disease		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003149167	SCV004294634	likely pathogenic	Maple syrup urine disease	2023-08-24	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. This variant disrupts the p.Leu194 amino acid residue in BCKDHB. Other variant(s) that disrupt this residue have been observed in individuals with BCKDHB-related conditions (PMID: 25748408, 30228974, 31980395), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BCKDHB protein function. ClinVar contains an entry for this variant (Variation ID: 2442395). This missense change has been observed in individual(s) with maple syrup urine disease (PMID: 25748408, 31980395). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 194 of the BCKDHB protein (p.Leu194Phe).