Submissions for variant NM_017780.4(CHD7):c.4795C>T (p.Gln1599Ter)

dbSNP: rs267606724

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000122607	SCV000329265	pathogenic	not provided	2015-07-21	criteria provided, single submitter	clinical testing	The Q1599X nonsense variant in the CHD7 gene has been reported previously as de novo in association with congenital heart disease (Zaidi et al., 2013). The Q1599X pathogenic variant has also been reported in a parent diagnosed with CHARGE syndrome and both of his affected children (Vuorela et al. 2007). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Q1599X 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. Approximately 45% of CHD7 pathogenic variants are nonsense changes predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay (Janssen et al., 2012; Zentner et al, 2010). Therefore, we interpret the Q1599X variant to be pathogenic.
OMIM	RCV000002118	SCV000022276	pathogenic	CHARGE association	2008-10-01	no assertion criteria provided	literature only
Richard Lifton Laboratory, Yale University School of Medicine	RCV000122607	SCV000155115	untested	not provided		no assertion provided	not provided	Converted during submission to not provided.