Submissions for variant NM_031407.7(HUWE1):c.12067C>T (p.Arg4023Cys)

dbSNP: rs1556914274

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital	RCV000498781	SCV000503013	likely pathogenic	Intellectual disability, X-linked syndromic, Turner type	2017-01-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002318372	SCV000850033	uncertain significance	Inborn genetic diseases	2016-06-27	criteria provided, single submitter	clinical testing	The p.R4023C variant (also known as c.12067C>T), located in coding exon 75 of the HUWE1 gene, results from a C to T substitution at nucleotide position 12067. The arginine at codon 4023 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000498781	SCV000993611	likely pathogenic	Intellectual disability, X-linked syndromic, Turner type	2019-03-29	criteria provided, single submitter	research
GeneDx	RCV001547214	SCV001766868	likely pathogenic	not provided	2024-03-13	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: 29180823, 36111624, 36307859, 31957018, 36353900)
CeGaT Center for Human Genetics Tuebingen	RCV001547214	SCV003917795	likely pathogenic	not provided	2023-03-01	criteria provided, single submitter	clinical testing	HUWE1: PM2, PS4:Moderate, PP2, PP3, PP4
OMIM	RCV000498781	SCV000902280	pathogenic	Intellectual disability, X-linked syndromic, Turner type	2006-06-15	no assertion criteria provided	literature only