Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001069870 | SCV001235067 | pathogenic | Multiple congenital exostosis | 2019-01-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr553Thrfs*68) in the EXT1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EXT1-related conditions. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). |
| Victorian Clinical Genetics Services, |
RCV002471030 | SCV002766968 | pathogenic | Exostoses, multiple, type 1 | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with multiple exostoses type 1 (MIM#133700). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Variable intrafamilial expressivity resulting in clinically undiagnosed cases due to absent or unidentified mild symptoms have been reported (PMIDs: 9326317, 29529714). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Multiple NMD-predicted variants have been classified as likely pathogenic or pathogenic (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 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 |