ClinVar Miner

Submissions for variant NM_000127.3(EXT1):c.538_539del (p.Leu181fs)

dbSNP: rs886039486
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254961 SCV000322126 pathogenic not provided 2016-02-22 criteria provided, single submitter clinical testing The c.538_539delAG pathogenic variant in the EXT1 gene has been reported previously in association with hereditary multiple exostoses (Jennes et al., 2008; Reijnders et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.538_539delAG variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000538727 SCV000626131 pathogenic Multiple congenital exostosis 2023-01-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 265339). This premature translational stop signal has been observed in individual(s) with multiple osteochondromas (PMID: 18165274, 20813973, 22116208). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu181Profs*7) in the EXT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120).
Fulgent Genetics, Fulgent Genetics RCV002494802 SCV002804383 pathogenic Chondrosarcoma; Exostoses, multiple, type 1 2021-09-28 criteria provided, single submitter clinical testing

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