ClinVar Miner

Submissions for variant NM_001918.5(DBT):c.1202T>C (p.Ile401Thr)

gnomAD frequency: 0.00001  dbSNP: rs1449113689
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000668260 SCV001575139 likely pathogenic Maple syrup urine disease 2021-09-25 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 401 of the DBT protein (p.Ile401Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals with maple syrup urine disease (PMID: 19480318). ClinVar contains an entry for this variant (Variation ID: 552910). 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 DBT protein function. 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.
Genome-Nilou Lab RCV000668260 SCV002033175 likely pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568514 SCV004190857 likely pathogenic Maple syrup urine disease type 1A 2024-03-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526740 SCV005040287 uncertain significance not specified 2024-03-14 criteria provided, single submitter clinical testing Variant summary: DBT c.1202T>C (p.Ile401Thr) results in a non-conservative amino acid change located in the 2-oxoacid dehydrogenase acyltransferase, catalytic domain (IPR001078) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251378 control chromosomes (gnomAD). c.1202T>C has been reported in the literature in individuals affected with Maple Syrup Urine Disease (Gorzelany_2009). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 19480318). ClinVar contains an entry for this variant (Variation ID: 552910). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005004334 SCV005632858 likely pathogenic Maple syrup urine disease type 2 2024-03-16 criteria provided, single submitter clinical testing
Counsyl RCV000668260 SCV000792833 uncertain significance Maple syrup urine disease 2017-07-18 flagged submission clinical testing

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