ClinVar Miner

Submissions for variant NM_014297.5(ETHE1):c.427G>A (p.Val143Ile)

gnomAD frequency: 0.00002  dbSNP: rs201846162
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen RCV000551325 SCV002037597 uncertain significance Ethylmalonic encephalopathy 2020-08-18 reviewed by expert panel curation This variant was classified as a variant of uncertain significance as there has not been sufficient evidence to support either a benign or a pathogenic classification. Specifically, this variant has not been reported in the literature in affected or unaffected patients, has no published functional data. This variant is present in population databases with an allele frequency of 0.09%, which is higher allele frequency expected for a pathogenic variant in ETHE1 (BS1). However, not enough criteria were met to support a pathogenic or benign classification.
Labcorp Genetics (formerly Invitae), Labcorp RCV000551325 SCV000645213 uncertain significance Ethylmalonic encephalopathy 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 143 of the ETHE1 protein (p.Val143Ile). This variant is present in population databases (rs201846162, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with ETHE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 468478). 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 not expected to disrupt ETHE1 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.
Natera, Inc. RCV000551325 SCV001456211 uncertain significance Ethylmalonic encephalopathy 2019-10-28 no assertion criteria provided clinical testing

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