ClinVar Miner

Submissions for variant NM_016120.4(RLIM):c.1159C>T (p.Arg387Cys)

dbSNP: rs1569309776
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
CeGaT Center for Human Genetics Tuebingen RCV002292497 SCV002585133 likely pathogenic not provided 2022-08-01 criteria provided, single submitter clinical testing RLIM: PM1, PM2, PS4:Moderate, PP3, PS3:Supporting
Ambry Genetics RCV002518541 SCV003739367 likely pathogenic Inborn genetic diseases 2020-11-04 criteria provided, single submitter clinical testing The c.1159C>T (p.R387C) alteration is located in exon 5 (coding exon 3) of the RLIM gene. This alteration results from a C to T substitution at nucleotide position 1159, causing the arginine (R) at amino acid position 387 to be replaced by a cysteine (C). Based on data from the Genome Aggregation Database (gnomAD), the RLIM c.1159C>T alteration was not observed, with coverage at this position. This alteration has been observed to co-segregate with disease in a three generation family through 5 affected males and 9 carrier females. One affected male died in the newborn period from a lethal unspecified congenital heart malformation and surviving males presented with mild to moderate intellectual disability, short stature, microcephaly, variable behavioral problems, and dysmorphic features. Carrier females were reported to have normal cognition and behavior, but mild skeletal features such as short stature, pes planus, and broad stubby thumbs with short distal phalanges compared to non-carrier sisters. Two of these females were reported with primary ovarian insufficiency (Frints, 2019; Hu, 2016). The p.R387 amino acid is conserved in available vertebrate species. Functional analysis demonstrated that the p.R387C alteration was unable to rescue the phenotype of a knockout zebrafish animal model, which the wild type protein could rescue successfully. It is suggested that ubiquitination of a target protein, REX1, is affected by the p.R387C alteration but the described effect has been conflicting (Bustos, 2018; Frints, 2019) The in silico prediction for the p.R387C alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.
OMIM RCV000239497 SCV000297886 pathogenic Intellectual disability, X-linked 61 2018-10-11 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.