Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521374 | SCV000617840 | pathogenic | not provided | 2017-09-22 | criteria provided, single submitter | clinical testing | The R709X variant in the RASA1 gene has been reported in at least four unrelated individuals with CV-AVM, three of whom had affected family members who also harbored the R709X variant (Revencu et al., 2008; Revencu et al., 2016; Grillner et al., 2016). R709X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the RASA1 gene have been reported in Human Gene Mutation Database in association with CV-AVM (Stenson et al., 2014). Furthermore, the R709X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). |
Invitae | RCV001386102 | SCV001586205 | pathogenic | Capillary malformation-arteriovenous malformation syndrome | 2022-08-10 | 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 create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 449560). This premature translational stop signal has been observed in individuals with capillary malformation-arteriovenous malformations (CM-AVM) (PMID: 18446851, 24038909, 26499346, 29024832). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg709*) in the RASA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RASA1 are known to be pathogenic (PMID: 24038909). |