Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV001251216 | SCV001426703 | likely pathogenic | Hereditary spastic paraplegia 30 | 2020-06-15 | criteria provided, single submitter | curation | This variant is interpreted as likely pathogenic for spastic paraplegia 30, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (PM5); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease (PP2). |
Paris Brain Institute, |
RCV001251216 | SCV001451082 | pathogenic | Hereditary spastic paraplegia 30 | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV001879816 | SCV002205746 | pathogenic | Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9 | 2023-05-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 974913). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg167 amino acid residue in KIF1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25265257, 26410750, 34487232). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 KIF1A protein function. This missense change has been observed in individuals with autosomal dominant hereditary spastic paraplegia (PMID: 31488895, 34487232). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 167 of the KIF1A protein (p.Arg167His). |
Ce |
RCV002511065 | SCV002821052 | pathogenic | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | KIF1A: PS2, PM2, PM5:Supporting, PP2, PP3, PS1:Supporting |