ClinVar Miner

Submissions for variant NM_024757.5(EHMT1):c.2873_2876TTCT[1] (p.Ser960fs) (rs786205129)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483684 SCV000566450 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing The c.2877_2880delTTCT deletion in the EHMT1 gene has been reported previously in association withKleefstra syndrome. This variant was observed as a de novo finding in an individual with intellectualdisability, seizures, brain abnormalities, and hearing impairment (Willemsen et al., 2012). Thec.2877_2880delTTCT deletion causes a frameshift starting with codon Serine 960, changes this aminoacid to a Glycine residue and creates a premature Stop codon at position 7 of the new reading frame,denoted p.Ser960Glyfsx7. This variant is predicted to cause loss of normal protein function either throughprotein truncation or nonsense-mediated mRNA decay. The c.2877_2880delTTCT variant was notobserved in approximately 6,500 individuals of European and African American ancestry in the NHLBIExome Sequencing Project, indicating it is not a common benign variant in these populations. We interpretc.2877_2880delTTCT as a pathogenic variant.
Invitae RCV000055964 SCV000823080 pathogenic Chromosome 9q deletion syndrome 2017-09-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser960Glyfs*7) in the EHMT1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with Kleefstra syndrome (PMID: 22670141). ClinVar contains an entry for this variant (Variation ID: 65734). Loss-of-function variants in EHMT1 are known to be pathogenic (PMID: 16826528, 19264732). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000055964 SCV000087004 pathogenic Chromosome 9q deletion syndrome 2015-05-07 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.