ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.1424T>A (p.Leu475His)

gnomAD frequency: 0.00001  dbSNP: rs764935677
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001246010 SCV001419337 uncertain significance Congenital myasthenic syndrome 4A 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 475 of the CHRNE protein (p.Leu475His). This variant is present in population databases (rs764935677, gnomAD 0.0009%). 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: 970439). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. RCV001835254 SCV002093366 uncertain significance Congenital myasthenic syndrome 2020-01-24 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004548098 SCV004727182 uncertain significance CHRNE-related disorder 2023-10-30 no assertion criteria provided clinical testing The CHRNE c.1424T>A variant is predicted to result in the amino acid substitution p.Leu475His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-4802089-A-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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