Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000032221 | SCV005086205 | pathogenic | Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss | 2023-07-17 | 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 likely mechanisms of disease in this gene, and are associated with macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (MIM#155100) and autosomal dominant deafness 17 (MIM#603622) (PMIDs: 20301740, 32545517). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Expressivity varies for onset and severity of sensorineural deafness, glomerular nephropathy, presenile cataract, and alterations of liver enzymes (PMID: 20301740). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to leucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated myosin tail 1 (DECIPHER). (I) 0703 - Another missense variant comparable to the one identified in this case has moderate previous evidence for pathogenicity. p.(Arg1165Cys) has been reported as pathogenic by many clinical testing laboratories (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least five unrelated individuals with MYH9-related disease, and hearing loss has also been reported in some of those individuals (PMIDs: 11776386, 26226608, 33217855, 33718801). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Gene |
RCV000032221 | SCV000055827 | not provided | Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss | no assertion provided | literature only | Associated with high risk for hearing loss and low risk for nephropathy and cataract |