Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001149469 | SCV001310425 | likely benign | Autosomal dominant cerebellar ataxia | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Labcorp Genetics |
RCV001882459 | SCV002270900 | uncertain significance | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1468 of the ITPR1 protein (p.Val1468Ile). This variant is present in population databases (rs200646875, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ITPR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 902723). 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 ITPR1 protein function with a negative predictive value of 95%. 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. |
| Gene |
RCV001882459 | SCV002512839 | uncertain significance | not provided | 2022-04-15 | criteria provided, single submitter | clinical testing | Reported in the heterozygous state in an individual with gait ataxia, spasticity, resting tremor and hydrocephalus and this individual's father with shuffling gait, dementia and normal pressure hydrocephalus (Tipton et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27908616) |
| Ambry Genetics | RCV004032773 | SCV004890364 | uncertain significance | Inborn genetic diseases | 2023-10-16 | criteria provided, single submitter | clinical testing | Unlikely to be causative of ITPR1-related congenital non-progressive spinocerebellar ataxia (AD), Gillespie syndrome (AD) or ITPR1-related spinocerebellar ataxia (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Centre de Biologie Pathologie Génétique, |
RCV001251780 | SCV001427522 | likely benign | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing |