Submissions for variant NM_017780.4(CHD7):c.5428C>T (p.Arg1810Ter)

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Total submissions: 5

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000548285	SCV000631259	pathogenic	CHARGE association	2019-12-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1810*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. 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 has been reported in the literature in individuals affected with CHARGE syndrome (PMID: 16400610, 26538304, 18445044). In several of these individuals, the variant was shown to be de novo (PMID: 16400610). ClinVar contains an entry for this variant (Variation ID: 459555). This variant is not present in population databases (ExAC no frequency).
GeneDx	RCV000599382	SCV000709800	pathogenic	not provided	2023-07-27	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 (gnomAD); This variant is associated with the following publications: (PMID: 26538304, 16400610, 33100332, 18445044, 35938004, 29261186, 25525159)
Provincial Medical Genetics Program of British Columbia, University of British Columbia	RCV000548285	SCV002320801	pathogenic	CHARGE association	2022-01-01	criteria provided, single submitter	clinical testing
3billion	RCV000548285	SCV004013828	pathogenic	CHARGE association		criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. It is a stop-gained (nonsense) variant 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: VCV000459555/PMID: 16400610). This variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000548285	SCV004046360	pathogenic	CHARGE association		criteria provided, single submitter	clinical testing	This nonsense variant found in exon 26 of 38 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported in patients with CHARGE syndrome, as a de novo change or of unknown inheritance (PMID: 16400610, 26538304, 18445044). It is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.5428C>T (p.Arg1810Ter) variant is classified as Pathogenic.

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