Submissions for variant NM_014297.5(ETHE1):c.61G>T (p.Ala21Ser)

gnomAD frequency: 0.01995  dbSNP: rs116440799

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen	RCV000288835	SCV001736739	benign	Ethylmalonic encephalopathy	2021-05-06	reviewed by expert panel	curation	The allele frequency of the c.61G>T variant in the ETHE1 gene is 0.7% in gnomAD, including 33 homozygotes which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen ETHE1 Variant Curation Expert Panel (>0.1% in gnomAD- BA1 and BS2). In summary, this variant meets criteria to be classified as benign for ETHE1-related ethylmalonic encephalopathy. ETHE1 specific ACMG/AMP criteria applied: (BA1, BS2).
GeneDx	RCV000124925	SCV000168365	benign	not specified	2014-03-17	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224357	SCV000280916	likely benign	not provided	2015-05-21	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Illumina Laboratory Services, Illumina	RCV000288835	SCV000413494	benign	Ethylmalonic encephalopathy	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000288835	SCV000645214	benign	Ethylmalonic encephalopathy	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000288835	SCV001157052	benign	Ethylmalonic encephalopathy	2023-11-29	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000224357	SCV000802235	benign	not provided	2016-03-16	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000288835	SCV002088910	benign	Ethylmalonic encephalopathy	2019-11-28	no assertion criteria provided	clinical testing