Submissions for variant NM_015267.4(CUX2):c.1768G>A (p.Glu590Lys)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000709621	SCV000890027	likely pathogenic	Developmental and epileptic encephalopathy, 67	2016-05-18	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000709621	SCV000930060	likely pathogenic	Developmental and epileptic encephalopathy, 67	2019-02-27	criteria provided, single submitter	curation	This variant is interpreted as a Likely pathogenic for Epileptic encephalopathy, early infantile, 67, autosomal dominant. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate : PS4 downgraded in strength to Moderate (Variant absent from controls and recurrent in multiple unrelated patients PMID:28628100,23020937,29630738,29795476). PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM6-Strong : PM6 upgraded in strength to Strong (Assumed de novo in multiple unrelated patients PMID:28628100,23020937,29630738,29795476).
GeneDx	RCV001662782	SCV001874933	pathogenic	not provided	2024-09-26	criteria provided, single submitter	clinical testing	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: 33057194, 35982159, 34758253, 23020937, 28191890, 30842224, 24866042, 29630738, 28628100, 29795476)
Baylor Genetics	RCV000709621	SCV003835539	pathogenic	Developmental and epileptic encephalopathy, 67	2022-09-04	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000709621	SCV004022283	pathogenic	Developmental and epileptic encephalopathy, 67	2023-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003420268	SCV004115796	pathogenic	CUX2-related disorder	2022-11-29	criteria provided, single submitter	clinical testing	The CUX2 c.1768G>A variant is predicted to result in the amino acid substitution p.Glu590Lys. This variant has been repeatedly reported to occur de novo in individuals with nonsyndromic intellectual disability (see for example at Rauch et al. 2012. PubMed ID: 23020937, described as chr12: g.111748354G>A at Table 4 and Supplementary Table S2 & S8; Kosmicki et al. 2017. PubMed ID: 28191890, Supplementary Table 2; Geisheker et al. 2017. PubMed ID: 28628100, Suppl. Table 4; Iwama et al. 2019. PubMed ID: 30842224). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.
OMIM	RCV000709621	SCV000839537	pathogenic	Developmental and epileptic encephalopathy, 67	2020-11-24	no assertion criteria provided	literature only
Genomics England Pilot Project, Genomics England	RCV000709621	SCV001760294	likely pathogenic	Developmental and epileptic encephalopathy, 67		no assertion criteria provided	clinical testing
Molecular Genetics laboratory, Necker Hospital	RCV001662782	SCV004031380	pathogenic	not provided	2021-04-12	no assertion criteria provided	clinical testing