ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.3398C>T (p.Thr1133Met)

dbSNP: rs1064793083
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479619 SCV000564866 uncertain significance not provided 2023-06-23 criteria provided, single submitter clinical testing Identified in one proband in large cohort of individuals with neurodevelopmental disorders in published literature; however, no further phenotypic information was provided (Stessman et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26436962, 26813943, 30653986, 28191889)
Ambry Genetics RCV000624092 SCV000741087 pathogenic Inborn genetic diseases 2015-10-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763600 SCV000894445 likely pathogenic CHARGE association; Hypogonadotropic hypogonadism 5 with or without anosmia 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001366746 SCV001563061 uncertain significance CHARGE association 2023-11-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1133 of the CHD7 protein (p.Thr1133Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CHD7-related conditions (PMID: 26436962, 30653986). ClinVar contains an entry for this variant (Variation ID: 418124). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CHD7 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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