Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001582388 | SCV001821400 | likely pathogenic | Hemochromatosis type 1 | 2021-08-27 | criteria provided, single submitter | clinical testing | Variant summary: HFE c.691_693delTAC (p.Tyr231del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 3.6e-05 in 251484 control chromosomes (gnomAD). c.691_693delTAC has been reported in the literature in a 43-year-old homozygous man who was diagnosed as having Hereditary haemochromatosis. His 42-year-old sister who was also homozygous for the variant, had no clinical symptoms at the time of the examination; she was noted however with suggested presence of a slight iron accumulation in the liver (Takano_2011). These data indicate that the variant may be associated with disease. Experimental evidence evaluating an impact on protein function demonstrated the variant leads to defective HFE traffic to the cell surface and was associated with inadequate hepcidin expression (Vecchi_2010). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |