creators_name: McCormick, Elizabeth M.
creators_name: Lott,  Marie T.
creators_name: Dulik, Matthew C.
creators_name: Shen, Lishuang
creators_name: Attimonelli,  Marcella
creators_name: Vitale, Ornella
creators_name: Karaa, Amel
creators_name: Bai, Renkui
creators_name: Pineda-Alvarez, Daniel E
creators_name: Singh, Larry N.
creators_name: Stanley,  Christine M
creators_name: Wong, Stacey
creators_name: Bhardwaj, Anshu
creators_name: Merkurjev, Daria
creators_name: Mao,  Rong
creators_name: Sondheimer, Neal
creators_name: Zhang, Shiping
creators_name: Procaccio, Vincent
creators_name: Wallace, Douglas C
creators_name: Gai, Xiaowu
creators_name: Falk,  Marni J.
type: article
datestamp: 2020-11-27 06:57:24
lastmod: 2020-11-27 06:57:39
metadata_visibility: show
title: Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation
ispublished: pub
subjects: QR
keywords: criteria;heteroplasmy;mitochondria;mtDNA;pathogenicity;variant interpretation
note: The copyright of this article belongs to Wiley.
abstract: Mitochondrial DNA (mtDNA) variant pathogenicity interpretation has special considerations given unique features of the mtDNA genome, including maternal inheritance, variant heteroplasmy, threshold effect, absence of splicing, and contextual effects of haplogroups. Currently, there are insufficient standardized criteria for mtDNA variant assessment, which leads to inconsistencies in clinical variant pathogenicity reporting. An international working group of mtDNA experts was assembled within the Mitochondrial Disease Sequence Data Resource Consortium and obtained Expert Panel status from ClinGen. This group reviewed the 2015 American College of Medical Genetics and Association of Molecular Pathology standards and guidelines that are widely used for clinical interpretation of DNA sequence variants and provided further specifications for additional and specific guidance related to mtDNA variant classification. These Expert Panel consensus specifications allow for consistent consideration of the unique aspects of the mtDNA genome that directly influence variant assessment, including addressing mtDNA genome composition and structure, haplogroups and phylogeny, maternal inheritance, heteroplasmy, and functional analyses unique to mtDNA, as well as specifications for utilization of mtDNA genomic databases and computational algorithms.
date: 2020-11-10
date_type: published
publication: Human Mutation
publisher: Wiley
refereed: TRUE
official_url: https://onlinelibrary.wiley.com/toc/10981004/0/0
citation:   McCormick, Elizabeth M. and Lott, Marie T. and Dulik, Matthew C. and Shen, Lishuang and Attimonelli, Marcella and Vitale, Ornella and Karaa, Amel and Bai, Renkui and Pineda-Alvarez, Daniel E and Singh, Larry N. and Stanley, Christine M and Wong, Stacey and Bhardwaj, Anshu and Merkurjev, Daria and Mao, Rong and Sondheimer, Neal and Zhang, Shiping and Procaccio, Vincent and Wallace, Douglas C and Gai, Xiaowu and Falk, Marni J.  (2020) Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation.  Human Mutation.