Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002221392 | SCV002498626 | uncertain significance | Aortic valve disease 3 | 2021-08-10 | criteria provided, single submitter | clinical testing | This sequence change in ROBO4 is predicted to replace arginine with cysteine at codon 491 (p.(Arg491Cys)). The arginine residue is weakly conserved (100 vertebrates, UCSC), and is not located in an annotated functional domain. There is a large physicochemical difference between arginine and cysteine. The highest population minor allele frequency in gnomAD v2.1 is 0.03% (11/19,894 alleles) in the East Asian population. This variant has been reported as likely benign (LOVD). To our knowledge, this variant has not been reported in the literature in any individuals with aortic valve disease. Multiple lines of computational evidence have conflicting predictions for the missense substitution (4/6 algorithms predict benign). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: none. |