Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493700 | SCV000582619 | likely pathogenic | not provided | 2015-11-18 | criteria provided, single submitter | clinical testing | The H441R variant in the COMP gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The H441R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H441R variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (D437G, D439N, D439E, G440R, G440E, D446N, D446H) have been reported in the Human Gene Mutation Database in association with pseudoachondroplasia and multiple epiphyseal dysplasia (Stenson et al., 2014), supporting the functional importance of this region of the protein. The H441R variant is a strong candidate for a pathogenic variant |