Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001066055 | SCV001231049 | pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 | 2024-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 142 of the RAPSN protein (p.Ala142Asp). This variant is present in population databases (rs368695664, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of congenital myasthenic syndrome (PMID: 14729848, 19620612; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 859852). 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 RAPSN protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001559969 | SCV001782297 | likely pathogenic | not provided | 2025-03-18 | criteria provided, single submitter | clinical testing | 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: 14729848, 22678886, 38511267, 19620612, 37334785) |
| Revvity Omics, |
RCV001559969 | SCV002019021 | likely pathogenic | not provided | 2021-11-08 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797818 | SCV002041681 | uncertain significance | not specified | 2021-11-03 | criteria provided, single submitter | clinical testing | Variant summary: RAPSN c.425C>A (p.Ala142Asp) results in a non-conservative amino acid change located in the MalT-like TPR region domain (IPR041617) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249160 control chromosomes. c.425C>A has been reported in the literature as a compound heterozygous genotype in at-least two individuals affected with Congenital Myasthenic Syndrome (example, Ohno_2004, Milone_2009). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. One laboratory classified the variant as likely pathogenic and one laboratory classified the variant as uncertain significance citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV003467832 | SCV004206097 | likely pathogenic | Fetal akinesia deformation sequence 2 | 2023-08-05 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005049757 | SCV005684660 | likely pathogenic | Congenital myasthenic syndrome 11; Fetal akinesia deformation sequence 2 | 2024-02-10 | criteria provided, single submitter | clinical testing |