Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001038425 | SCV001201892 | pathogenic | Multiple congenital exostosis | 2019-02-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in an individual affected with multiple osteochondromas (PMID: 16088908). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln2*) in the EXT1 gene. It is expected to result in an absent or disrupted protein product. |
| 3billion | RCV003152746 | SCV003841341 | pathogenic | Exostoses, multiple, type 1 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with EXT1 related disorder (ClinVar ID: VCV000837149 / PMID: 16088908). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV003473617 | SCV004192775 | pathogenic | Chondrosarcoma | 2022-09-06 | criteria provided, single submitter | clinical testing |