Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001937875 | SCV002177805 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 180 of the RAPSN protein (p.Glu180Lys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of RAPSN-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 1407774). 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 not expected to disrupt RAPSN protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genetics and Molecular Pathology, |
RCV002466711 | SCV002761931 | uncertain significance | Fetal akinesia deformation sequence 2 | 2022-05-09 | criteria provided, single submitter | clinical testing | The RAPSN c.538G>A variant is classified as a VARIANT OF UNCERTAIN SIGNFICANCE (PM2, PM3, PP2) The RAPSN c.538G>A variant is a single nucleotide change in exon 3/8 of the RAPSN gene, which is predicted to change the amino acid glutamic acid at position 180 in the protein to lysine. The variant is rare in population databases (gnomAD allele frequency = 0.0013%; 2 het and 0 hom in 152234 sequenced alleles; highest frequency = 0.0029%, Non-Finnish European population) (PM2). This is a missense variant in the constrained TPR5 region of the RAPSN gene and missense variants are a common mechanism of disease (PP2). This variant has been detected in trans with p.(Glu147Lys) in this patient (PM3). Computational predictions provide conflicting interpretations of pathogenicity for this variant (PP3 and BP4 not met). The variant has been reported in dbSNP (rs1452482859). It has not been reported in ClinVar or HGMD. |