Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV001093444 | SCV001250429 | likely pathogenic | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV001093444 | SCV001713722 | likely pathogenic | not provided | 2021-01-15 | criteria provided, single submitter | clinical testing | PS3, PM2, PP3, PP5 |
| ARUP Laboratories, |
RCV001093444 | SCV002506101 | likely pathogenic | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | The SLC4A1 c.2608C>T; p.Arg870Trp variant (rs28931585), also known as band 3 Prague III, is reported in the literature in three individuals affected with spherocytosis (Andolfo 2021, Bracher 2001, Jarolim 1995). In vitro functional analyses demonstrate that the mutant protein is unable to incorporate into cell membranes (Quilty 2000). This variant is also reported in ClinVar (Variation ID: 17776). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 870 is highly conserved and computational analyses predict that this variant is deleterious (REVEL: 0.907). Based on available information, this variant is considered to be likely pathogenic. REFERENCES Andolfo I et al. Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients. Genes (Basel). 2021 Jun 23. PMID: 34201899 Bracher NA et al. Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III. Br J Haematol. 2001 Jun. PMID: 11380459 Jarolim P et al. Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis. Blood. 1995 Feb 1. PMID: 7530501 Quilty JA et al. Trafficking and folding defects in hereditary spherocytosis mutants of the human red cell anion exchanger. Traffic. 2000 Dec. PMID: 11208088 |
| Invitae | RCV001093444 | SCV003442386 | pathogenic | not provided | 2023-07-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 870 of the SLC4A1 protein (p.Arg870Trp). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC4A1 protein function. ClinVar contains an entry for this variant (Variation ID: 17776). This variant is also known as Prague III. This missense change has been observed in individuals with autosomal dominant hereditary spherocytosis (PMID: 7530501, 23255290). This variant is not present in population databases (gnomAD no frequency). |
| Revvity Omics, |
RCV001093444 | SCV004238672 | likely pathogenic | not provided | 2023-07-24 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000019354 | SCV000039644 | pathogenic | Hereditary spherocytosis type 4 | 2001-06-01 | no assertion criteria provided | literature only |