Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001942222 | SCV002228214 | pathogenic | not provided | 2021-07-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with spherocytosis (PMID: 29572776, 31122244). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg286*) in the ANK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANK1 are known to be pathogenic (PMID: 8640229). |
| Gene |
RCV001942222 | SCV002818631 | pathogenic | not provided | 2022-07-05 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33868383, 32436265, 31122244, 34335240, 31602632, 29572776, 29396846) |
| Mayo Clinic Laboratories, |
RCV001942222 | SCV004227645 | pathogenic | not provided | 2022-11-23 | criteria provided, single submitter | clinical testing | PM2, PM6, PS4_moderate, PVS1 |
| Revvity Omics, |
RCV003490972 | SCV004237190 | pathogenic | Hereditary spherocytosis type 1 | 2023-07-20 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV003490972 | SCV004563770 | pathogenic | Hereditary spherocytosis type 1 | 2023-09-13 | criteria provided, single submitter | clinical testing | The ANK1 c.856C>T; p.Arg286Ter variant, also known as p.Arg319Ter, is reported in the literature in at least six individuals affected with spherocytosis (Wang 2018, Russo 2018, Choi 2019, Aggarwal 2020, Tole 2020 and Wu 2021) and is reported in ClinVar (Variation ID: 1455153). This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Aggarwal A et al. Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next-generation sequencing: First South Asian study. Br J Haematol. 2020 Mar. PMID: 31602632 Choi HS et al. Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte. Orphanet J Rare Dis. 2019 May 23. PMID: 31122244 Russo R et al. Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias. Am J Hematol. 2018 May. PMID: 29396846 Tole S et al. Genotype-phenotype correlation in children with hereditary spherocytosis. Br J Haematol. 2020 Nov. PMID: 32436265 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776 Wu C et al. Preliminary Study on the Clinical and Genetic Characteristics of Hereditary Spherocytosis in 15 Chinese Children. Front Genet. 2021 PMID: 33868383 |