Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000114347 | SCV000814779 | pathogenic | Aicardi-Goutieres syndrome 5 | 2023-07-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 126406). This premature translational stop signal has been observed in individual(s) with Aicardi-Goutieres syndrome (PMID: 19525956). This variant is present in population databases (rs369587937, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg442*) in the SAMHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SAMHD1 are known to be pathogenic (PMID: 19525956, 22461318). |
| Illumina Laboratory Services, |
RCV000114347 | SCV000915940 | uncertain significance | Aicardi-Goutieres syndrome 5 | 2017-04-28 | criteria provided, single submitter | clinical testing | The SAMHD1 c.1324C>T (p.Arg442Ter) variant is a stop-gained variant that is predicted to cause premature termination of the protein. The p.Arg442Ter variant has been reported in one study in which it is found in one patient with Aicardi-Goutieres syndrome in a compound heterozygous state with a missense variant (Rice et al. 2009). Control data are unavailable for this variant, which is also not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Functional studies with the p.Arg442Ter variant transfected into HEK293 cells demonstrate that the variant does not affect the RNA binding function of the protein (Goncalves et al. 2012). Based on the limited evidence and the potential impact of stop-gained variants, the p.Arg442Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for Aicardi-Goutieres syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Revvity Omics, |
RCV001781440 | SCV002019986 | pathogenic | not provided | 2019-07-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000114347 | SCV000147923 | not provided | Aicardi-Goutieres syndrome 5 | no assertion provided | literature only |