Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004790045 | SCV005399309 | likely pathogenic | Arthrogryposis, distal, with impaired proprioception and touch | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Likely pathogenic. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene. Loss of function has been associated with NMD variants while gain of function has been associated with missense variants clustered in the C-terminal (PMID: 30988732). (N) 0108 - This gene is known to be associated with both recessive and dominant disease. Dominant variants are generally missense and are clustered at the C-terminal (PMID: 30988732). (N) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine (exon 46). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (P) 0600 - Variant is located in an annotated domain or motif. In the PIEZO_RRAS binding domain (DECIPHER, NCBI, PDB) (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1102 - Strong phenotype match. (P) 1204 - Variant shown to be de novo in proband (parental status not tested but assumed). (P) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |