Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001960707 | SCV002235038 | pathogenic | Joubert syndrome 20; Meckel syndrome, type 11 | 2025-01-06 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 3 of the TMEM231 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TMEM231 are known to be pathogenic (PMID: 23012439, 23349226). This variant is present in population databases (rs752141701, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of TMEM231-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 1454613). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV001960707 | SCV005646204 | likely pathogenic | Joubert syndrome 20; Meckel syndrome, type 11 | 2024-01-10 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV005361866 | SCV005918251 | likely pathogenic | Ciliopathy | 2023-05-10 | criteria provided, single submitter | research | |
Prevention |
RCV004756329 | SCV005362393 | likely pathogenic | TMEM231-related disorder | 2024-08-29 | no assertion criteria provided | clinical testing | The TMEM231 c.741+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD. Variants that disrupt the consensus splice donor site in TMEM231 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |