ClinVar Miner

Submissions for variant NM_000709.4(BCKDHA):c.511del (p.Leu171fs)

dbSNP: rs762084007
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000601066 SCV000731950 likely pathogenic Maple syrup urine disease 2017-10-05 criteria provided, single submitter clinical testing The p.Leu171TrpfsX159 (NM_000709.3 c.511delC) variant in BCKDHA has not been pre viously reported in individuals with maple syrup urine disease. It has been iden tified in 3/30782 South Asian chromosomes by the Genome Aggregation Database (ht tp://gnomad.broadinstitute.org; rs762084007). This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at posit ion 171 and leads to a premature termination codon 159 amino acids downstream. T his alteration is then predicted to lead to a truncated or absent protein. Biall elic loss of function of the BCKDHA gene is associated with maple syrup urine di sease. In summary, although additional studies are required to fully establish a null impact, the p.Leu171TrpfsX159 variant is likely pathogenic for maple syrup urine disease in an autosomal recessive manner based on its predicted impact on the protein. ACMG/AMP Criteria applied: PVS1; PM2 (Richards 2015).
Invitae RCV000601066 SCV000819977 pathogenic Maple syrup urine disease 2023-10-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu171Trpfs*159) in the BCKDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCKDHA are known to be pathogenic (PMID: 16786533, 22593002). This variant is present in population databases (rs762084007, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with maple syrup urine disease (PMID: 31980395). ClinVar contains an entry for this variant (Variation ID: 517592). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000601066 SCV002033384 pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000601066 SCV004215916 pathogenic Maple syrup urine disease 2023-03-15 criteria provided, single submitter clinical testing

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