Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institut IMAGINE, |
RCV000709992 | SCV000678259 | pathogenic | Neurodegeneration with brain iron accumulation | 2016-05-02 | criteria provided, single submitter | research | The homozygous c.962G>A variant (p.Arg321His) in CRAT is a rare SNP (rs138665095, ExAc: A=0.0042%) that has never been reported to be homozygous in the control population. It alters a highly conserved amino acid residue. The variant was absent from 110 NBIA subject and 200 control chromosomes. |
Equipe Genetique des Anomalies du Developpement, |
RCV000594657 | SCV000966148 | likely pathogenic | Neurodegeneration with brain iron accumulation 8 | 2018-10-29 | criteria provided, single submitter | clinical testing | Observed as a homozygote. |
Invitae | RCV002531113 | SCV003460782 | uncertain significance | not provided | 2022-07-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 321 of the CRAT protein (p.Arg321His). This variant is present in population databases (rs138665095, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with neurodegeneration with brain iron accumulation (PMID: 29395073). ClinVar contains an entry for this variant (Variation ID: 503495). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
OMIM | RCV000594657 | SCV000709669 | pathogenic | Neurodegeneration with brain iron accumulation 8 | 2018-03-27 | no assertion criteria provided | literature only |