Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509183 | SCV002819808 | uncertain significance | not specified | 2022-12-25 | criteria provided, single submitter | clinical testing | Variant summary: CP c.1123T>C (p.Tyr375His) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251210 control chromosomes. To our knowledge, no occurrence of c.1123T>C in individuals affected with Neurodegeneration With Brain Iron Accumulation/aceruloplasminemia has been reported. At least one publication reports experimental evidence evaluating an impact on protein function (Kono_2010). The most pronounced variant effect results in failure to stabilize cell surface Ferroportin because of impaired the ferroxidase activity (approximately 20% of WT) which is required for Ferroportin stability. 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 VUS-possibly pathogenic. |
Gene |
RCV000034955 | SCV000058575 | pathologic | Deficiency of ferroxidase | 2013-04-18 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |