Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000991800 | SCV001143561 | likely pathogenic | not provided | 2019-04-17 | criteria provided, single submitter | clinical testing | The best available variant frequency is uninformative because it is below the disease allele frequency. Found in at least one symptomatic patient. Located in potentially critical domain of the protein. Damaging to protein function(s) relevant to disease mechanism. |
| Invitae | RCV001351372 | SCV001545836 | likely pathogenic | Congenital myasthenic syndrome 4A | 2023-12-14 | criteria provided, single submitter | clinical testing | This variant, c.529_531del, results in the deletion of 1 amino acid(s) of the CHRNE protein (p.Glu177del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs779816027, gnomAD 0.003%). This variant has been observed in individual(s) with clinical features of autosomal recessive congenital myasthenic syndrome (CMS) (PMID: 15145336; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as E157del. ClinVar contains an entry for this variant (Variation ID: 804695). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects CHRNE function (PMID: 15145336). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV000991800 | SCV002032722 | pathogenic | not provided | 2022-10-31 | criteria provided, single submitter | clinical testing | In-frame deletion of 1 amino acid in a non-repeat region; Published functional studies demonstrate a damaging effect, as expression of E177del in human embryonic kidney cells results in loss of AChR surface expression (Burke et al., 2004); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15145336) |
| Baylor Genetics | RCV001351372 | SCV004214236 | likely pathogenic | Congenital myasthenic syndrome 4A | 2023-07-28 | criteria provided, single submitter | clinical testing |