{"id":666,"date":"2024-02-13T23:00:00","date_gmt":"2024-02-13T23:00:00","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=87d9a51015b826cf06a3b44d5e996569"},"modified":"2024-02-14T02:19:45","modified_gmt":"2024-02-14T02:19:45","slug":"phenotypic-compatibility-and-specificity-in-genomic-variant-classification","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2024\/02\/13\/phenotypic-compatibility-and-specificity-in-genomic-variant-classification\/","title":{"rendered":"Phenotypic compatibility and specificity in genomic variant classification"},"content":{"rendered":"European Journal of Human Genetics, Published online: 13 February 2024;\n\nGenome-wide sequencing for monogenic conditions for clinical purposes is used in two main settings: 1) preventive pre-conceptional, newborn, and healthy adult screening; and 2) diagnostic prenatal and postnatal testing. Reported genomic variants are categorized as diagnostic, secondary, incidental, or reproduction-related. Historically, diagnostic testing primarily targeted individuals identified by their phenotypes. However, recent years have witnessed a shift towards a \u201cgenotyping-first approach\u201d, prompted largely by the decreasing costs of sequencing, particularly when balanced against the time clinicians spend characterizing phenotypes as well as the availability of clinicians to perform in-depth phenotyping.\n\nHowever, as establishing phenotypic specificity and compatibility with a variant is essential for both classifying the variant and linking it to a patient\u2019s clinical presentation, genotyping without prior phenotyping could have an impact on variant classification and case interpretation [<a id=\"ref-link-section-d42032351e304\" title=\"Chopra M, Savatt JM, Bingaman TI, Good ME, Morgan A, Cooney C, et al. Clinical variants paired with phenotype: A rich resource for brain gene curation. Genet Med. 2023; \n                https:\/\/doi.org\/10.1016\/j.gim.2023.101035\n\n              .\" href=\"https:\/\/www.nature.com\/articles\/s41431-024-01554-6#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,\u00a0<a id=\"ref-link-section-d42032351e307\" title=\"Basel-Salmon L, Orenstein N, Markus-Bustani K, Ruhrman-Shahar N, Kilim Y, Magal N, et al. Improved diagnostics by exome sequencing following raw data reevaluation by clinical geneticists involved in the medical care of the individuals tested. Genet Med. 2019;21:1443\u201351.\" href=\"https:\/\/www.nature.com\/articles\/s41431-024-01554-6#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a>]. Phenotype-genotype compatibility estimation might be further complicated by the suboptimal communication of detailed phenotypic information about the proband and the family members to the diagnostic laboratory [<a id=\"ref-link-section-d42032351e310\" title=\"Basel-Salmon L, Ruhrman-Shahar N, Orenstein N, Goldberg Y, Gonzaga-Jauregui C, Shuldiner AR, et al. When phenotype does not match genotype: importance of \u201creal-time\u201d refining of phenotypic information for exome data interpretation. Genet Med. 2021;23:215\u201321.\" href=\"https:\/\/www.nature.com\/articles\/s41431-024-01554-6#ref-CR3\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 3\">3<\/a>]. Moreover, a clear definition of what constitutes a \u201cspecific phenotype\u201d as well as a \u201ccompatible phenotype\u201d is still lacking.\n\n<a href=\"https:\/\/www.nature.com\/articles\/s41431-024-01554-6\">doi:10.1038\/s41431-024-01554-6<\/a>\n\nPhenotypic compatibility and specificity in genomic variant classification","protected":false},"excerpt":{"rendered":"<p>                European Journal of Human Genetics, Published online: 13 February 2024; doi:10.1038\/s41431-024-01554-6Phenotypic compatibility and specificity in genomic variant classification<\/p>\n","protected":false},"author":146,"featured_media":460,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,11],"tags":[62],"class_list":["post-666","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-articulos","category-eurjhumgen","tag-variantes"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/666","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/146"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=666"}],"version-history":[{"count":4,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/666\/revisions"}],"predecessor-version":[{"id":788,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/666\/revisions\/788"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media\/460"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=666"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=666"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=666"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}