Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000596696 | SCV000706499 | pathogenic | not provided | 2017-03-28 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000596696 | SCV001961438 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | OTX2: PVS1:Strong, PM2, PS4:Moderate, PM6:Supporting, PS3:Supporting |
| Victorian Clinical Genetics Services, |
RCV000594111 | SCV002768004 | pathogenic | Syndromic microphthalmia type 5 | 2022-03-31 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with syndromic microphthalmia 5 (MIM#610125). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance (PMID: 30268123). (I) 0115 - Variants in this gene are known to have variable expressivity. A wide range of inter- and intrafamilial phenotypic variability has been reported (PMID: 30268123). (I) 0204 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with at least 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant is predicted to lose the transactivation domain (PMID: 18628516). (I) 0701 - Other variants predicted to result in a truncated protein comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar, DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported as de novo in a patient with anophthalmia, short stature, and partial growth hormone deficiency (PMID: 18628516) and has also been reported as pathogenic in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional studies show that the mutant protein barely retained transactivation activities (PMID: 18628516). (SP) 1205 - This variant has been shown to be maternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Labcorp Genetics |
RCV003530088 | SCV004297099 | pathogenic | Anophthalmia-microphthalmia syndrome | 2023-08-02 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 500507). This variant is also known as p.L135fsX136. This premature translational stop signal has been observed in individual(s) with OTX2-related conditions (PMID: 18628516). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser135Leufs*2) in the OTX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 155 amino acid(s) of the OTX2 protein. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects OTX2 function (PMID: 18628516). |
| OMIM | RCV000594111 | SCV000044213 | pathogenic | Syndromic microphthalmia type 5 | 2008-10-01 | no assertion criteria provided | literature only |