Submissions for variant NM_004092.4(ECHS1):c.410_411del (p.Tyr137fs)

dbSNP: rs777218310

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487396	SCV000566185	uncertain significance	not provided	2023-10-10	criteria provided, single submitter	clinical testing	Reported in another patient with mitochondrial short chain enoyl-CoA hydratase 1 deficiency who was also heterozygous for another variant in ECHS1 (Aljishi et al., 2019); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28755360, 28409271, 28106320, 27905109, 28202214, 28039521, 27221955, 27090768, 26920905, 26099313, 26081110, 26000322, 25393721, 25125611, Aljishi2019[casereport], 31216405)
Ambry Genetics	RCV000623926	SCV000742868	pathogenic	Inborn genetic diseases	2017-10-03	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000850548	SCV000992760	pathogenic	Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	2017-12-31	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV000487396	SCV002501652	pathogenic	not provided	2021-07-07	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000487396	SCV002817273	pathogenic	not provided	2021-08-20	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual tested at Athena Diagnostics with clinical features associated with this gene.This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000487396	SCV003013170	pathogenic	not provided	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr137Cysfs*7) in the ECHS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ECHS1 are known to be pathogenic (PMID: 25393721, 26000322, 27090768). This variant is present in population databases (rs777218310, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ECHS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 418830). For these reasons, this variant has been classified as Pathogenic.