Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781466 | SCV000919512 | likely pathogenic | Hemochromatosis type 1 | 2018-07-06 | criteria provided, single submitter | clinical testing | Variant summary: HFE c.77-2_78delinsTGGAGTC is an alteration of a canonical splice-site and spanning into the exon2 of coding sequence. This variant is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 276792 control chromosomes. To our knowledge, no occurrence of c.77-2_78delinsTGGAGTC in individuals affected with Hemochromatosis type 1 and no experimental evidence demonstrating its impact on protein function have been reported. 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. |