Submissions for variant NM_017780.4(CHD7):c.3205C>T (p.Arg1069Ter)

dbSNP: rs886040985

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000258145	SCV000328329	pathogenic	CHARGE association	2016-09-05	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000258145	SCV000594104	pathogenic	CHARGE association	2016-08-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000760387	SCV000890252	pathogenic	not provided	2021-11-17	criteria provided, single submitter	clinical testing	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: 25525159, 30244528, 16400610, 29300383)
Fulgent Genetics, Fulgent Genetics	RCV000763599	SCV000894444	pathogenic	CHARGE association; Hypogonadotropic hypogonadism 5 with or without anosmia	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000258145	SCV001585635	pathogenic	CHARGE association	2023-07-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1069*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with CHARGE syndrome (PMID: 16400610, 29300383). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 267423). For these reasons, this variant has been classified as Pathogenic.
3billion	RCV000258145	SCV004013513	pathogenic	CHARGE association		criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000267423 / PMID: 16400610). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Sbielas Lab-Department of Human Genetics University of Michigan, University of Michigan Medical School	RCV000258145	SCV000680054	pathogenic	CHARGE association	2017-10-27	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000258145	SCV001197960	likely pathogenic	CHARGE association		no assertion criteria provided	research