Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Medical Genetics and Molecular Medicine, |
RCV000497788 | SCV000503003 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2017-01-18 | criteria provided, single submitter | clinical testing | |
Undiagnosed Diseases Network, |
RCV000497788 | SCV000863412 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2018-09-04 | criteria provided, single submitter | clinical testing | |
Equipe Genetique des Anomalies du Developpement, |
RCV000497788 | SCV001190300 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2019-08-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001571522 | SCV001796016 | pathogenic | not provided | 2020-12-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); 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: 32336296, 29180823, 29307790, 25985138) |
Mendelics | RCV000497788 | SCV002516566 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000497788 | SCV002766475 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2022-11-22 | criteria provided, single submitter | clinical testing | Variant summary: HUWE1 c.329G>A (p.Arg110Gln) results in a conservative amino acid change located in a domain of unknown function DUF908 (IPR010309) in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183017 control chromosomes (gnomAD). c.329G>A has been reported in the literature as a de novo variant in the heterozygous state in three female individuals affected with intellectual disability and craniosynostosis (e.g. Taylor_2015, Moortgat_2018). In all three cases, these individuals exhibited skewed X-inactivation of the wildtype X chromosome, resulting in preferential expression of the variant allele. These data indicate that the variant is likely associated with disease. Furthermore, a different missense change at the same amino acid, p.Arg110Trp, has been observed in at least one hemizygous male with similar clinical features (e.g. Taylor_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001571522 | SCV003445157 | pathogenic | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 110 of the HUWE1 protein (p.Arg110Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with HUWE1-related conditions (PMID: 25985138, 29180823). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 375709). 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. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002524683 | SCV003752368 | pathogenic | Inborn genetic diseases | 2020-10-09 | criteria provided, single submitter | clinical testing | The c.329G>A (p.R110Q) alteration is located in exon 6 (coding exon 3) of the HUWE1 gene. This alteration results from a G to A substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 to be replaced by a glutamine (Q). Based on data from the Genome Aggregation Database (gnomAD), the HUWE1 c.329G>A alteration was not observed, with coverage at this position. This alteration was described as a recurrent de novo alteration in female patients with a neurodevelopmental syndrome that included motor delays, mild intellectual disability, skeletal anomalies, craniosynostosis, and facial dysmorphic features. All females showed skewed inactivation of the X chromosome favoring the affected allele (Taylor, 2015; Moortgat, 2018). The p.R110 amino acid is conserved in available vertebrate species. The p.R110Q alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. |
Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000497788 | SCV000863839 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2018-03-23 | no assertion criteria provided | clinical testing | |
OMIM | RCV000497788 | SCV000902279 | pathogenic | Intellectual disability, X-linked syndromic, Turner type | 2021-08-20 | no assertion criteria provided | literature only |