Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001329559 | SCV001521030 | likely pathogenic | Joubert syndrome 20 | 2019-07-12 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155395 | SCV003845101 | likely pathogenic | Joubert syndrome and related disorders | 2023-02-21 | criteria provided, single submitter | clinical testing | Variant summary: TMEM231 c.407G>A (p.Trp136X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 210808 control chromosomes (gnomAD). To our knowledge, no occurrence of c.407G>A in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV003770819 | SCV004576538 | pathogenic | Joubert syndrome 20; Meckel syndrome, type 11 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp136*) in the TMEM231 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TMEM231 are known to be pathogenic (PMID: 23012439, 23349226). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TMEM231-related conditions. ClinVar contains an entry for this variant (Variation ID: 1028502). For these reasons, this variant has been classified as Pathogenic. |