Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004790099 | SCV005400049 | uncertain significance | Arthrogryposis, distal, with impaired proprioception and touch | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with arthrogryposis (OMIM). Loss of function has generally been shown to be caused by NMD variants whereas gain of function has generally been associated with missense variants clustered in the C-terminal (PMID: 30988732). (I) 0108 - This gene is associated with both recessive and dominant disease. Recessive disease is due to loss of function variants and dominant disease is due to gain of function variants (PMID: 30988732). The phenotypes have been recently regarded as etiologically related (PMID: 24726473). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0705 - No comparable splice variants have previous evidence for pathogenicity. (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) 1102 - Strong phenotype match for this individual. (SP) 1205 - This variant has been shown to be maternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |