Table 2.

Outline of online web modules for classifying a Variant

Module	Section	Content/Purpose
What Does VUS mean	What is a Genetic Variant	Explains variation in human disease and the different ways they are classified
	Genetic Variants & Disease	Variants can be associated with increased or decreased risk for disease
	Understanding Rare Variants	Most rare variants are benign, and certain rare variants can be unique in families
	Medical Care and VUS	Guidelines suggest not to alter medical management given a VUS, but rather, consider family history and other risk factors when assessing risk.
	Reclassifying VUS	Sufficient evidence may determine if a VUS does or does not cause disease in the family and reclassification of the VUS to benign or likely pathogenic can occur.
Co-Segregation Analysis for Variant Classification	Information that can be used to classify a variant	This information includes, comparing variant to other variants, looking at how often this variant occurs in individuals with disease, comparing this variant across species
	Basics of using family information for co-segregation analysis:	Describes methods and likelihood ratios used when performing family studies to determine if a variant is associated with disease
	Evidence standards for variant classification	Reviews different levels of classification assigned to variants ranging from benign to pathogenic.
	Classifying a pathogenic variant	Provides description and illustration of a pedigree for a pathogenic variant at different sizes/stages of analysis
	Classifying a benign variant	Provides description and illustration of a pedigree for a benign variant at different sizes/stages of analysis
	Using other information to help classify a variant	How geneticists can compile many sources of information to determine a likelihood ration that a variant is traveling with disease in a family.
Talking with your immediate family about your variant	Start with what you already know	Instructs individuals to start by recording pertinent personal information
	Organize information about your immediate family	Teaches how to add known family history information about close relatives
	Add what you know about your extended family	Describes adding information about health and disease in extended family members
	Talking with your family	Instruct how to be sensitive to family members while communicating with them.
	Contact your living parents and siblings	Explains how to collect, record, and confirm basic facts about close relatives.
Using genealogy to identify ancestors who might have your variant	Talking with living relatives to find your ancestors	Teaches how to gather information from living relatives about deceased ancestors.
	Using online genealogy tools to find your ancestors	Lists several genealogy resources including major family history websites with a very brief description of how to use these resources.
	Obtaining tumors from deceased ancestors for testing	Introduces the potential option of getting tissue from pathology samples from deceased ancestors and briefly describes this process.
Finding and Connecting with distant relatives that might have your variant	Start with the people you know	Explains that the best way to find distant relatives is by starting with people that you already know
	Talking with living relatives to find descendants of your ancestors	Describes how to talk to known relatives about descendants of a common ancestor, including how to ask for contact information of distant relatives.
	Using online social networking sites to find descendants of your ancestors	Provides examples of how to use social networking sits, like Facebook, to identify distant relatives.
	Don’t forget low-tech	Lists several public search engines used for finding information about relatives and a variety of people search tools.
Laboratory Testing and asking relatives about participation in VUS classification	Finding a clinical Laboratory to Test Samples and Classify Your Variant	Lists family study resources offered by several clinical laboratories in the United States.
	Finding a Research Laboratory to Test Samples and Classify Your Variant	Lists contact information for research studies performing family studies for VUS reclassification.
	Asking Family Members to Help You Classify Your VUS	Different clinical laboratories and research studies have different processes for sample submission. This module instructs participants to contact the testing laboratory directly to find details about how relatives can submit samples and offers tips for approaching family.
	Example Scripts to Ask a Family Member to Help Classify a Variant	Provides text examples of how to ask a family member to donate a sample to help classify a VUS.
Genetics Education	What is a gene?	Lists websites that provides explanations and resources for genetics learning tools
	What is a variant?	Lists websites that explain normal variation across humans and provides links learning tools
	Where do our genes come from?	Lists websites that explain basic concepts of heredity and de novo mutations
	How does heredity work?	Lists websites that describe inheritance patterns in families and individuals
	What is a mutation?	Lists websites that describe what changes in DNA are and how they happen.