{"id":15003,"date":"2024-07-23T11:31:03","date_gmt":"2024-07-23T11:31:03","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=15003"},"modified":"2024-07-23T11:31:03","modified_gmt":"2024-07-23T11:31:03","slug":"2024-integration-of-validated-functional-evidence-to-support-the-pathogenicity-of-kcnh2-variants","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-integration-of-validated-functional-evidence-to-support-the-pathogenicity-of-kcnh2-variants\/","title":{"rendered":"2024 &#8211; Integration of validated functional evidence to support the pathogenicity of KCNH2 variants"},"content":{"rendered":"<p>Functional investigation of genetic variants found in long QT syndrome can provide evidence \u00a0needed to confirm the genetic diagnosis and establish the cause of the condition. We performed functional assessment to determine the Z-score, using a clinically calibrated \u00a0automated patch clamp assay, for two missense KCNH2 variants found in 2 families that have \u00a0been diagnosed with long QT syndrome. These variants are currently classified as variant of \u00a0uncertain significance in ClinVar. The Z-scores for homozygous and heterozygous \u00a0NM_000238.4:c.1819A&gt;T p.(Ile607Phe) from family 1 were \u20135.16 and \u20133.97, respectively, and \u00a0for heterozygous NM_000238.4:c.1832A&gt;G p.(Tyr611Cys) from family 2 was \u20136.63. The Z11 scores for these variants are consistent with severe loss-of-function phenotypes. We have established the genetic cause of the long QT syndrome in these two families by providing validated functional evidence that supports the pathogenicity of p.(Ile607Phe) and p.(Tyr611Cys). Clinical diagnosis of long QT syndrome has been very successful in providing adequate clinical management for patients. However, functional assessment of variants found in these patients by using variant-specific Z-scores can further enhance the current clinical management of patients with long QT syndrome through shared decision-making based on validated experimental evidence.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,53],"therapeutic_areas":[54,143],"target_categories":[61],"target_families":[333],"targets":[],"resource_keyword":[],"class_list":["post-15003","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","therapeutic_areas-cardiac-safety-cipa","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-kv-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/15003","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=15003"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=15003"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=15003"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=15003"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=15003"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=15003"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=15003"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=15003"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=15003"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}