Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001868315 | SCV002203798 | uncertain significance | Aortic valve disease 2 | 2021-08-26 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002470959 | SCV002768983 | uncertain significance | Craniosynostosis 7 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with aortic valve disease 2 (MIM#614823) and craniosynostosis 7 (MIM#617439). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. Variants associated with craniosynostosis have been reported to be inherited from clinically unaffected parents (PMIDs: 32499606, 27606499). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. It has been reported as uncertain pathogenicity in an individual with craniosynostosis (PMID: 32499606), and reported as a VUS in ClinVar. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1004 - This variant has moderate functional evidence supporting normal protein function. Functional studies using transfected cells showed normal inhibitory activity and normal protein stability (PMID: 32499606). (SB) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |