Submissions for variant NM_005327.5(HADH):c.676T>C (p.Tyr226His) (rs146036912)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000194052	SCV000223932	likely pathogenic	Deficiency of 3-hydroxyacyl-CoA dehydrogenase	2014-11-19	criteria provided, single submitter	clinical testing
Invitae	RCV000194052	SCV000937777	uncertain significance	Deficiency of 3-hydroxyacyl-CoA dehydrogenase	2018-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine with histidine at codon 226 of the HADH protein (p.Tyr226His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs146036912, ExAC 0.01%). This variant has been reported in combination with another HADH variant in an individual affected with M/SCHAD deficiency (PMID: 16725361). This variant is also known as p.Y214H in the literature. ClinVar contains an entry for this variant (Variation ID: 212734). Experimental studies have shown that this missense change abrogates HADH enzyme activity  (PMID: 16725361). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.