Submissions for variant NM_031407.7(HUWE1):c.9208C>T (p.Arg3070Cys)

dbSNP: rs886041876

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000406579	SCV000330662	pathogenic	not provided	2022-11-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29180823, 32336296, 31130284, 33710394, 33504798)
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital	RCV000497622	SCV000503011	likely pathogenic	Intellectual disability, X-linked syndromic, Turner type	2017-01-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000497622	SCV000894494	pathogenic	Intellectual disability, X-linked syndromic, Turner type	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000406579	SCV000959934	pathogenic	not provided	2022-06-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 HUWE1 protein function. ClinVar contains an entry for this variant (Variation ID: 280723). This missense change has been observed in individual(s) with HUWE1-related disease (PMID: 29180823). 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 arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3070 of the HUWE1 protein (p.Arg3070Cys).
Center for Statistical Genetics, Columbia University	RCV001261371	SCV001438281	pathogenic	Intellectual disability	2020-10-16	criteria provided, single submitter	research
Revvity Omics, Revvity	RCV000497622	SCV002016653	likely pathogenic	Intellectual disability, X-linked syndromic, Turner type	2021-03-25	criteria provided, single submitter	clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV002274008	SCV002558978	pathogenic	Neurodevelopmental delay		criteria provided, single submitter	clinical testing
3billion	RCV000497622	SCV002572643	pathogenic	Intellectual disability, X-linked syndromic, Turner type	2022-09-01	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.87; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000280723). A different missense change at the same codon (p.Arg3070His) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000841299). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV000497622	SCV002574868	pathogenic	Intellectual disability, X-linked syndromic, Turner type	2022-09-22	criteria provided, single submitter	clinical testing
Duke University Health System Sequencing Clinic, Duke University Health System	RCV000497622	SCV003918961	pathogenic	Intellectual disability, X-linked syndromic, Turner type	2023-04-20	criteria provided, single submitter	research