Submissions for variant NM_003865.3(HESX1):c.308T>A (p.Leu103Ter)

gnomAD frequency: 0.00001  dbSNP: rs777223697

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627251	SCV000748242	likely pathogenic	not provided	2018-04-20	criteria provided, single submitter	clinical testing	The L103X variant in the HESX1 gene has been reported previously in the heterozygous state in a child with septo-optic dysplasia, however, no clinical information was provided and it is unknown if the variant was associated with autosomal dominant or recessive inheritance (Mueller et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The L103X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret L103X as a likely pathogenic variant.
CeGaT Center for Human Genetics Tuebingen	RCV000627251	SCV001246951	likely pathogenic	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000581553	SCV000692275	pathogenic	Septo-optic dysplasia sequence	2009-06-22	no assertion criteria provided	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000582144	SCV000692276	pathogenic	Pituitary hormone deficiency, combined, 1	2009-06-22	no assertion criteria provided	clinical testing