Submissions for variant NM_000127.3(EXT1):c.357C>A (p.Tyr119Ter)

dbSNP: rs119103289

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002468956	SCV002765639	pathogenic	not provided	2022-06-13	criteria provided, single submitter	clinical testing	Reported in a patient with multiple osteochondromas in published literature (Raskind et al., 1998); however, clinical data is limited; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10679937, 9521425)
Neuberg Centre For Genomic Medicine, NCGM	RCV000002605	SCV005060877	likely pathogenic	Exostoses, multiple, type 1		criteria provided, single submitter	clinical testing	The stop gained c.357C>A (p.Tyr119Ter) variant in the EXT1 gene has been reported previously in a patient with multiple osteochondromas (Raskind et al., 1998). This variant is absent in the gnomAD Exomes. It is submitted to ClinVar as Pathogenic. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. The nucleotide change c.357C>A in EXT1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Evidence in multiple individuals and additional studies are required to prove the pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic.
OMIM	RCV000002605	SCV000022763	pathogenic	Exostoses, multiple, type 1	1998-01-01	no assertion criteria provided	literature only