ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.3655C>T (p.Arg1219Ter) (rs372174845)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000303888 SCV000329261 pathogenic not provided 2015-12-28 criteria provided, single submitter clinical testing The R1219X nonsense variant in the CHD7 gene has been reported previously in association with CHARGE syndrome (Jongmans et al., 2006; Writzl et al., 2007; Bilan et al., 2012). 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). Additionally, the variant 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. Therefore, the presence of the R1219X pathogenic variant is consistent with a diagnosis of CHARGE syndrome
Invitae RCV000509342 SCV000824604 pathogenic CHARGE association 2019-06-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1219*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with CHARGE syndrome or individuals referred for CHD7 testing (PMID: 16155193, 28475860, 21158681, 20884005). ClinVar contains an entry for this variant (Variation ID: 279759). Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect, ClinGen RCV000509342 SCV000606943 not provided CHARGE association no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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