ClinVar Miner

Submissions for variant NM_007118.4(TRIO):c.4309A>G (p.Lys1437Glu)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004595112 SCV005087204 likely pathogenic Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome 2023-07-17 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with autosomal dominant intellectual developmental disorder with microcephaly (MIM#617061) and intellectual developmental disorder with macrocephaly (MIM#618825) (PMID: 32109419). (I) 0107 - This gene is associated with autosomal dominant disease. Null variants and missense variants located within the GEFD1 domain are associated with intellectual developmental disorder with microcephaly (MIM#617061), while missense variants within the 7th spectrin repeat are associated with intellectual developmental disorder with macrocephaly (MIM#618825; PMID: 32109419). (I) 0200 - Variant is predicted to result in a missense amino acid change from lysine to glutamic acid. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER) and located in the GEFD1 domain (PMID: 32109419). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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.