Submissions for variant NM_001918.5(DBT):c.327C>T (p.Thr109=)

gnomAD frequency: 0.00078  dbSNP: rs138796800

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000192508	SCV000247160	uncertain significance	not specified	2014-06-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000322581	SCV000346208	uncertain significance	Maple syrup urine disease	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000756009	SCV000523248	likely benign	not provided	2018-05-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756009	SCV000883705	likely benign	not provided	2018-04-20	criteria provided, single submitter	clinical testing	The c.327C>T; p.Thr109Thr variant (rs138796800, ClinVar variant ID 210824) does not alter the amino acid sequence of the DBT protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with mitochondrial disease in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 0.2% (identified on 56 out of 30,774 chromosomes, including one homozygote). Based on the available information, the c.327C>T variant is likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000322581	SCV001014405	likely benign	Maple syrup urine disease	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756009	SCV001745935	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	DBT: BP4, BP7
Clinical Genetics, Academic Medical Center	RCV000192508	SCV001921715	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000756009	SCV001929099	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000756009	SCV001968435	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003917747	SCV004735696	likely benign	DBT-related disorder	2019-10-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).