Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
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 |