ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.3082A>G (p.Ile1028Val)

dbSNP: rs121434338
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000081828 SCV000329259 pathogenic not provided 2023-03-02 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect; the I1028V variant causes a complete loss of function of CHD7 (Balasubramanian et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20884005, 16155193, 18073582, 25472840, 15300250, 22539353, 26563674, 22461308, 28475860, 21158681, 32914532, 34828433, 33189935)
Eurofins Ntd Llc (ga) RCV000081828 SCV000331477 pathogenic not provided 2013-08-27 criteria provided, single submitter clinical testing
Invitae RCV000002100 SCV000755739 pathogenic CHARGE syndrome 2022-12-06 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2022). This missense change has been observed in individual(s) with CHARGE syndrome (PMID: 15300250, 16155193, 18073582, 20884005, 21158681, 22539353). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1028 of the CHD7 protein (p.Ile1028Val). Experimental studies have shown that this missense change affects CHD7 function (PMID: 25472840). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
Fulgent Genetics, Fulgent Genetics RCV000763598 SCV000894443 pathogenic CHARGE syndrome; Hypogonadotropic hypogonadism 5 with or without anosmia 2018-10-31 criteria provided, single submitter clinical testing
Institute of Human Genetics, University Hospital Muenster RCV002287316 SCV002577988 pathogenic Hypogonadotropic hypogonadism 2022-05-31 criteria provided, single submitter clinical testing ACMG categories: PS1,PS4,PM2,PM5
Laboratory of Medical Genetics, University of Torino RCV000002100 SCV004171100 likely pathogenic CHARGE syndrome criteria provided, single submitter clinical testing
OMIM RCV000002100 SCV000022258 pathogenic CHARGE syndrome 2004-09-01 no assertion criteria provided literature only

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