Submissions for variant NM_000709.4(BCKDHA):c.420G>A (p.Thr140=)

gnomAD frequency: 0.00016  dbSNP: rs143608852

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000615226	SCV000727638	likely benign	not specified	2018-02-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000948473	SCV001094685	likely benign	Maple syrup urine disease	2024-01-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000948473	SCV001293104	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.
Genome-Nilou Lab	RCV000948473	SCV002033761	likely benign	Maple syrup urine disease	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002331080	SCV002630016	likely benign	Inborn genetic diseases	2024-03-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003905639	SCV004721382	likely benign	BCKDHA-related disorder	2019-06-10	criteria provided, single submitter	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).