Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001808278 | SCV002058939 | uncertain significance | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.647, PP3_P). A missense variant is a common mechanism associated with Cerebral arteriopathy (PP2_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
| Neuberg Centre For Genomic Medicine, |
RCV001808278 | SCV005382357 | uncertain significance | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense variant c.590G>A(p.Arg197Gln) in the HTRA1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.001% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance by multiple submitters. However, no details are available for independent assessment. The amino acid Arginine at position 197 is changed to a Glutamine changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen - Probably damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |