Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003556137 | SCV004297903 | pathogenic | not provided | 2024-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 298 of the KLF1 protein (p.Ala298Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive congenital hemolytic anemia (PMID: 24443441, 34227100). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56891). 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 KLF1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Department of Medical Genetics, |
RCV000050236 | SCV000082828 | pathogenic | BLOOD GROUP--LUTHERAN INHIBITOR; Congenital dyserythropoietic anemia type 4; FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 6 | no assertion criteria provided | not provided | Converted during submission to Pathogenic. | |
OMIM | RCV004777567 | SCV005367938 | pathogenic | ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE IVb | 2024-10-03 | no assertion criteria provided | literature only |