Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000420519 | SCV000521106 | likely pathogenic | not provided | 2023-01-06 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect, as kinetic analysis showed P265L prolongs burst open duration 2-fold by slowing the rate of channel closing (Ohno et al., 1997); 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: 32721234, 34426522, 31589614, 9158150) |
Invitae | RCV000698763 | SCV000827448 | pathogenic | Congenital myasthenic syndrome 4A | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 265 of the CHRNE protein (p.Pro265Leu). This variant is present in population databases (rs759226183, gnomAD 0.009%). This missense change has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 9158150; Invitae). 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 also known as epsilonP245L. ClinVar contains an entry for this variant (Variation ID: 381628). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CHRNE function (PMID: 9158150). For these reasons, this variant has been classified as Pathogenic. |
Ai |
RCV000420519 | SCV002501820 | likely pathogenic | not provided | 2021-08-13 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000420519 | SCV002770942 | likely pathogenic | not provided | 2022-11-21 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to segregate with autosomal recessive congenital myasthenic syndrome in at least one family, however, the available information does not rule out segregation due to chance. In some published literature, this variant is referred to as c.734C>T (p.P245L). Computational tools predict that this variant is damaging. |
Fulgent Genetics, |
RCV002502514 | SCV002786934 | likely pathogenic | Congenital myasthenic syndrome 4A; Congenital myasthenic syndrome 4C; Congenital myasthenic syndrome 4B | 2022-03-03 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000698763 | SCV004212577 | likely pathogenic | Congenital myasthenic syndrome 4A | 2023-10-10 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000420519 | SCV004224134 | likely pathogenic | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | PP1, PP3, PM2, PM3, PS3_moderate |