ClinVar Miner

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

dbSNP: rs121434338
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Total submissions: 8
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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
Labcorp Genetics (formerly Invitae), Labcorp RCV000002100 SCV000755739 pathogenic CHARGE syndrome 2022-12-06 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CHD7 function (PMID: 25472840). 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). This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 2022). 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.
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 RCV004584305 SCV002577988 pathogenic See cases 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
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000002100 SCV005090978 pathogenic CHARGE syndrome 2024-04-25 criteria provided, single submitter clinical testing PS4, PS3, PM1, PM2, PP3- This variant has been reported in ClinVar as Pathogenic by other laboratories (Variation ID 2022).In silico prediction tools estimated that the variant could be damaging for the protein function/stracture. It is not present in population databases (gnomAD no frequency). It is reported previously as causative (PMID: 15300250, 16155193, 18073582, 20884005, 21158681, 22539353). Functional studies support pathogenic effect (PMID: 25472840).
OMIM RCV000002100 SCV000022258 pathogenic CHARGE syndrome 2004-09-01 no assertion criteria provided literature only

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