Submissions for variant NM_000182.5(HADHA):c.1981C>T (p.Leu661=)

gnomAD frequency: 0.00450  dbSNP: rs142348718

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078335	SCV000110181	benign	not specified	2018-08-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000386562	SCV000429497	likely benign	Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000294603	SCV000429498	likely benign	Mitochondrial trifunctional protein deficiency	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV001082488	SCV000645774	benign	Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588853	SCV000695945	benign	not provided	2017-04-10	criteria provided, single submitter	clinical testing	Variant summary: The HADHA c.1981C>T (p.Leu661Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 517/121374 control chromosomes (including 4 homozygotes) at a frequency of 0.0042596, which is approximately 2.2 times the estimated maximal expected allele frequency of a pathogenic HADHA variant (0.0019365), suggesting this variant is likely a benign polymorphism. It is more common in European (Non-Finnish) subpopulation with allele frequency of 0.006 (441/66716) including all reported homozygotes. One clinical diagnostic laboratory in ClinVar has classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.
GeneDx	RCV000588853	SCV000724404	benign	not provided	2020-06-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588853	SCV001501262	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	HADHA: BP4, BP7, BS2
Genetic Services Laboratory, University of Chicago	RCV000078335	SCV002068161	likely benign	not specified	2020-03-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588853	SCV004562752	benign	not provided	2023-10-19	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000386562	SCV001452958	likely benign	Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	2019-11-11	no assertion criteria provided	clinical testing