Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779064 | SCV000915530 | uncertain significance | RAPSN-related disorder | 2017-10-24 | criteria provided, single submitter | clinical testing | The RAPSN c.1029_1045delGGAACTGCGGGCGCACG (p.Glu344CysfsTer127) variant results in a frameshift, and is predicted to result in elongation of the protein. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for RAPSN-related disorders. |
| Labcorp Genetics |
RCV001232917 | SCV001405490 | pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 | 2023-07-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 632161). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RAPSN protein in which other variant(s) (p.Cys355*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with RAPSN-related conditions. This variant is present in population databases (rs765096923, gnomAD 0.01%). This sequence change results in a frameshift in the RAPSN gene (p.Glu344Cysfs*127). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acid(s) of the RAPSN protein and extend the protein by 57 additional amino acid residues. |
| Baylor Genetics | RCV003461050 | SCV004206121 | pathogenic | Fetal akinesia deformation sequence 2 | 2023-12-29 | criteria provided, single submitter | clinical testing |