Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000530418 | SCV000652858 | pathogenic | Joubert syndrome 20; Meckel syndrome, type 11 | 2017-11-20 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 3-6 of the TMEM231 gene. The 5' boundary is likely confined to intron 2. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has been observed in trans with a pathogenic TMEM231 variant in multiple affected individuals in a family with TMEM231-related disease (Invitae). A missense substitution in exon 4 (p.Asp262Asn) has been determined to be pathogenic (PMID: 23012439, 27449316). This suggests that the aspartic acid residue is critical for TMEM231 protein function, and that variants that disrupt this residue, including this deletion, may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |