ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.1291G>C (p.Ala431Pro)

dbSNP: rs121909517
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001382552 SCV001581389 pathogenic Congenital myasthenic syndrome 4A 2023-09-27 criteria provided, single submitter clinical testing 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CHRNE protein function. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CHRNE function (PMID: 10962020). ClinVar contains an entry for this variant (Variation ID: 18361). This missense change has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 10962020). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121909517, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 431 of the CHRNE protein (p.Ala431Pro).
Baylor Genetics RCV001382552 SCV004214232 pathogenic Congenital myasthenic syndrome 4A 2023-08-10 criteria provided, single submitter clinical testing
GeneDx RCV004786275 SCV005401382 pathogenic not provided 2024-05-07 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant disturbs ion channel function (PMID: 10962020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10962020, 31589614)
OMIM RCV000020029 SCV000040327 pathogenic Congenital myasthenic syndrome 4B 2000-09-01 no assertion criteria provided literature only

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