Submissions for variant NM_017780.4(CHD7):c.5833C>T (p.Arg1945Ter)

dbSNP: rs757160222

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000258138	SCV000328343	pathogenic	CHARGE association	2016-09-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000414205	SCV000491184	pathogenic	not provided	2021-06-29	criteria provided, single submitter	clinical testing	Apparently de novo variant in a patient with multiple congenital anomalies (Jongmans et al., 2006); 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 (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27321065, 25525159, 16400610, 27535533, 16155193, 32978145, 32804436)
Invitae	RCV000258138	SCV000755733	pathogenic	CHARGE association	2021-02-21	criteria provided, single submitter	clinical testing	This variant has been reported to be de novo in individuals affected with CHARGE syndrome and in other individuals affected with this disease (PMID: 16155193, 16400610, 21158681). ClinVar contains an entry for this variant (Variation ID: 267434). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg1945*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product.
CeGaT Center for Human Genetics Tuebingen	RCV000414205	SCV001747564	pathogenic	not provided	2023-11-01	criteria provided, single submitter	clinical testing	CHD7: PVS1, PS2, PS4, PM2