Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000641732 | SCV000763380 | pathogenic | Congenital myasthenic syndrome 4A | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 98 of the CHRNE protein (p.Leu98Pro). This variant is present in population databases (rs28929768, gnomAD 0.01%). For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt CHRNE protein function. ClinVar contains an entry for this variant (Variation ID: 534249). This missense change has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 30124556; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. |
Gene |
RCV001771872 | SCV001994728 | uncertain significance | not provided | 2021-03-18 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 12141316, 19153382, 30124556) |
Lifecell International Pvt. |
RCV000641732 | SCV003845979 | likely pathogenic | Congenital myasthenic syndrome 4A | criteria provided, single submitter | clinical testing | A Heterozygous Missense variant c.293T>C in Exon 4 of the CHRNE gene that results in the amino acid substitution p.Leu98Pro was identified. The observed variant allele frequency of 0.00002/0.00 % in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is medium, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Likely Pathogenic (ClinVar ID: 534249). This missense change has been observed in individual(s) with congenital myasthenic syndrome (Selvam P et al., 2018). Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines. | |
Oxford Medical Genetics Laboratories, |
RCV003325970 | SCV003853415 | pathogenic | Congenital myasthenic syndrome 4C | 2023-03-23 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000641732 | SCV004212567 | likely pathogenic | Congenital myasthenic syndrome 4A | 2023-10-19 | criteria provided, single submitter | clinical testing |