ClinVar Miner

Submissions for variant NM_001205254.2(OCLN):c.173_194del (p.Trp58fs)

dbSNP: rs797045841
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192882 SCV000248375 pathogenic Pseudo-TORCH syndrome 1 2015-07-23 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000192882 SCV000923659 pathogenic Pseudo-TORCH syndrome 1 2019-01-01 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000192882 SCV001164426 uncertain significance Pseudo-TORCH syndrome 1 2018-12-03 criteria provided, single submitter research The homozygous p.Trp58PhefsTer10 variant in OCLN was identified by our study in one individual with pseudo-torch syndrome. This variant was absent from large population studies. The homozygous variant was also reported in two Turkish siblings with pseudo-torch syndrome (PMID: 20727516). This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 58 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. At least two loss of function variants across multiple exons have been reported in association with pseudo-torch syndrome in ClinVar. Loss of function of the OCLN gene is a moderately established disease mechanism in autosomal recessive pseudo-torch syndrome. O'Driscoll et al. reported that five out of the six families with pseudo-torch syndrome in their study had variants that impacted the conserved MARVEL protein domain, which is associated with localization to the cellular membrane (PMID: 20727516). This suggests that variants in the MARVEL domain may not be tolerated. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PVS1_Moderate, PM1_Supporting (Richards 2015).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268371 SCV001447255 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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