Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498689 | SCV000589851 | likely pathogenic | not provided | 2016-05-17 | criteria provided, single submitter | clinical testing | The G426S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G426S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G426S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded |
| Invitae | RCV001851371 | SCV002247002 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 426 of the SMPD1 protein (p.Gly426Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with acid sphingomyelinase deficiency (PMID: 27338287). ClinVar contains an entry for this variant (Variation ID: 432163). 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 SMPD1 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000665319 | SCV000789419 | likely pathogenic | Niemann-Pick disease, type A | 2017-01-31 | no assertion criteria provided | clinical testing |