Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471487 | SCV002768198 | likely pathogenic | Loeys-Dietz syndrome 1 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely pathogenic. Following criteria are met: 0103 - Loss of function resulting from premature termination codon variants is a known mechanism of disease in this gene. In addition, missense variants have been postulated to exert a dominant negative effect. Both mechanisms are associated with Loeys-Dietz syndrome (MIM#609192) (PMID: 29706644; 21358634). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from lysine to glutamic acid. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER) within the protein kinase domain (PDB). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has previously been reported as likely pathogenic in one individual with no additional information provided (Decipher) and also in a family with thoracic aortic aneurysm and dissection (Shariant, personal communication). (SP) 0902 - This variant has moderate evidence for segregation with disease. This variant was shown to segregate with disease in one family with thoracic aortic aneurysm and dissection (Shariant, personal communication). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |