ClinVar Miner

Submissions for variant NM_000096.4(CP):c.1123T>C (p.Tyr375His)

dbSNP: rs386134128
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
GeneReviews RCV000034955 SCV000058575 pathologic Deficiency of ferroxidase 2013-04-18 no assertion criteria provided curation Converted during submission to Pathogenic.

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