Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002513050 | SCV003572129 | uncertain significance | Inborn genetic diseases | 2021-09-29 | criteria provided, single submitter | clinical testing | The c.1574T>C (p.I525T) alteration is located in exon 18 (coding exon 18) of the GPI gene. This alteration results from a T to C substitution at nucleotide position 1574, causing the isoleucine (I) at amino acid position 525 to be replaced by a threonine (T). Based on data from gnomAD, the C allele has an overall frequency of <0.01% (7/251366) total alleles studied. The highest observed frequency was 0.02% (6/30616) of South Asian alleles. This alteration has been reported in the homozygous state in patients with chronic anemia and reduced GPI activity (Walker, 1993; Fermo, 2019). This amino acid position is highly conserved in available vertebrate species. In vitro expression studies in E.coli showed that p.I525T significantly reduced residual enzyme activity and dimer fraction in response to SDS compared to wild type (Lin, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| OMIM | RCV000014611 | SCV000034866 | pathogenic | Hemolytic anemia due to glucophosphate isomerase deficiency | 1993-03-01 | no assertion criteria provided | literature only |