Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000990153 | SCV001140990 | pathogenic | BLOOD GROUP--LUTHERAN INHIBITOR | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001507932 | SCV001713782 | pathogenic | not provided | 2020-06-22 | criteria provided, single submitter | clinical testing | PS3, PS2, PS4_moderate, PM1, PM2, PP3 |
Revvity Omics, |
RCV001507932 | SCV002016382 | pathogenic | not provided | 2019-11-20 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV000009567 | SCV002073128 | pathogenic | Congenital dyserythropoietic anemia type 4 | criteria provided, single submitter | clinical testing | The missense variant p.E325K in KLF1 (NM_006563.5) has been previously reported in dominant state with congenital dyseryhtropoietic anemia (Arnaud L et al). Functional studies reveal a damaging effect. The variant has been submitted to ClinVar as Pathogenic. The p.E325K variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.E325K missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glutamic acid residue at codon 325 of KLF1 is conserved in all mammalian species. The nucleotide c.973 in KLF1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. | |
Labcorp Genetics |
RCV001507932 | SCV002151095 | pathogenic | not provided | 2021-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 325 of the KLF1 protein (p.Glu325Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals with clinical features of congenital dyserythropoietic anemia (PMID: 21055716, 23522491, 28102861, 29200155, 29300242, 29396846). ClinVar contains an entry for this variant (Variation ID: 18447). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects KLF1 function (PMID: 21055716, 21778342). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000009567 | SCV000029785 | pathogenic | Congenital dyserythropoietic anemia type 4 | 2013-01-01 | no assertion criteria provided | literature only |