Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV004762497 | SCV005372598 | uncertain significance | not provided | 2023-06-16 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
| Victorian Clinical Genetics Services, |
RCV004787161 | SCV005400566 | likely pathogenic | Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome | 2024-10-08 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with combined oxidative phosphorylation deficiency 31 (MIM#617228) (PMID:34620555, 27799064). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (21 heterozygotes, 0 homozygotes). (SP) 0708 - Other NMD variants comparable to the one identified in this case have conflicting previous evidence for pathogenicity. Four other NMD variants in this gene have been classified as either VUS or likely pathogenic/pathogenic in ClinVar, and two NMD variants have been observed in trans with missense variants that are classified as VUS (ClinVar, PMID: 27799064). (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |