ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.1453C>T (p.Leu485Phe)

gnomAD frequency: 0.00001  dbSNP: rs1085307690
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489356 SCV000577043 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing The L485F variant in the CHRNE gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L485F variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L485F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L485F as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001344117 SCV001538153 uncertain significance Congenital myasthenic syndrome 4A 2024-06-17 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 485 of the CHRNE protein (p.Leu485Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 426568). 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 CHRNE protein function with a negative predictive value of 95%. 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. RCV001276663 SCV001463157 uncertain significance Congenital myasthenic syndrome 2020-09-16 no assertion criteria provided clinical testing

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