Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004789924 | SCV005398352 | pathogenic | X-linked sideroblastic anemia 1 | 2024-10-08 | 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 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with sideroblastic anaemia 1 (MIM#300751; PMID: 34781359) and erythropoietic protoporphyria (MIM#300752; PMID: 23263862), respectively. (I) 0108 - This gene is associated with both X-linked recessive and dominant disease (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity. Variable severity has been reported for sideroblastic anaemia (OMIM). (I) 0217 - Non-coding variant with known effect. Analysis of patients' samples demonstrated both a reduction in mRNA by RT-qPCR and protein levels by western blotting (PMIDs: 24166784, 28123038) . (SP) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0601 - Variant is located in the well-established functional GATA motif within the promoter region. Deletion of this motif led to a reduction in GATA1 binding and subsequent ALAS2 protein expression (PMID: 28123038). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been identified in at least six families with hemizygous males affected with congenital sideroblastic anaemia (PMID: 23935018, 24166784, 28123038). (SP) 1102 - Strong phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |