ClinVar Miner

Submissions for variant NM_000127.3(EXT1):c.1421T>A (p.Leu474Ter)

dbSNP: rs1811893325
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070256 SCV001235476 pathogenic Multiple congenital exostosis 2019-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu474*) 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 nonsense change has been observed in individuals affected with multiple osteochondromatosis (PMID: 16283885, Invitae). 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. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). For these reasons, this variant has been classified as Pathogenic.

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