Heidi L. Rehm

TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.

TL;DR: It is recommended that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here and encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.

TL;DR: The key challenges of assessing sequence variants in human disease are discussed, integrating both gene-level and variant-level support for causality and guidelines for summarizing confidence in variant pathogenicity are proposed.

TL;DR: A patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication, and a different variant is found that is determined to be pathogenic.

TL;DR: The American College of Medical Genetics and Genomics has developed the following professional standards and guidelines to assist clinical laboratories with the validation ofNext-generation sequencing methods and platforms, the ongoing monitoring of next- generation sequencing testing to ensure quality results, and the interpretation and reporting of variants found using these technologies.