Submissions for variant NM_004092.4(ECHS1):c.814C>T (p.Arg272Trp)

gnomAD frequency: 0.00002  dbSNP: rs772585791

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001934675	SCV002133909	uncertain significance	not provided	2021-08-26	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with tryptophan at codon 272 of the ECHS1 protein (p.Arg272Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with ECHS1-related conditions. 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 ECHS1 protein function. 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.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003228009	SCV003924348	uncertain significance	Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	2023-05-08	criteria provided, single submitter	research