Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001265821 | SCV001443993 | uncertain significance | Inborn genetic diseases | 2018-07-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001880101 | SCV002123851 | likely benign | not provided | 2024-10-10 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV001880101 | SCV003820082 | uncertain significance | not provided | 2023-08-24 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001880101 | SCV004224670 | uncertain significance | not provided | 2022-10-06 | criteria provided, single submitter | clinical testing | PM2, PM3 |
| Victorian Clinical Genetics Services, |
RCV004789501 | SCV005400274 | uncertain significance | Hereditary spherocytosis type 3 | 2023-07-17 | 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: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with elliptocytosis-2 (HE; MIM#130600), pyropoikilocytosis (HPP; MIM#266140) and spherocytosis, type 3 (HS; MIM#270970). (I) 0108 - This gene is associated with both recessive and dominant disease. Autosomal dominant HE are caused by variants resulting in structural defects, mostly located within the a-0 spectrin repeat (PMID: 18218854). HE-causing variants combined with low expression variants frequently results in HPP (PMID: 27667160). Finally, HS is a result of severe deficiency of a-spectrin (PMID: 31364155). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 31364155). (I) 0200 - Variant is predicted to result in a missense amino acid change from lysine to asparagine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2: 29 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated spectrin-13 repeat (UniProt). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. It has been found in cis with c.4339-99C>T in two unrelated compound heterozygotes with HS (PMID: 31723846), in cis with c.4339-99C>T in an HS individual where a variant on the 2nd allele was not identified (PMID: 31040790) and heterozygous in two HS individuals with homozygous c.4339-99C>T (PMIDs: 35845192, 31147440). In addition, it is also heterozygous in an HS individual with other causative variants identified though phasing was not confirmed (PMID: 35845192). (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 |