Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471532 | SCV002768280 | uncertain significance | Platelet-type bleeding disorder 15 | 2022-03-31 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Loss of function (LoF) and gain of function (GoF) are reported mechanisms of disease in this gene and are associated with congenital macrothrombocytopenia (MIM#615193). LoF and GoF have been reported for missense variants, while the mechanism of disease for null variants is unclear (PMIDs: 23434115, 30351444, 26879394, 31365757). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0213 - In-frame deletion in a non-repetitive region that has high conservation. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0601 - Variant is located in the well-established functional CH2 domain. The CH2 domain binds in tandem with CH1 to form the actin binding domain in ACTN1 and facilitates high affinity binding to F-actin (DECIPHER, PMID: 32478077). (SP) 0705 - No comparable in-frame deletion 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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |