Please note this is a beta version of the ClinGen Evidence Repository. This resource is intended to provide access to variant level evidence used and applied by ClinGen Variant Curation Expert Panels in the classification of variants. In this beta version, the evidence is limited to curation notes and referenced literature (PMIDs).

For general information about ClinGen Expert Panels and Variant Curation please visit: Clinical Domain Working Groups. For specific inquiries regarding a variant classification or evidence curation (e.g. population database queried, segregation counts or other evidence used) or to submit general comments about the evidence repo, please email us.

The resource is undergoing updates and tesing. Should you encounter any issues regarding the data displayed, lack of functionality or other problems, please let us know so we can rectify these accordingly. Your help in this regard is greatly appreciated.

MYH7-associated inherited cardiomyopathies - adapted from ACMG/AMP

Stand Alone
Very Strong
Population Data

Allele frequency is >= 0.1% based on the filtering allele frequency (FAF) in ExAC BA1

Allele frequency is >=0.02% based on the filtering allele frequency (FAF) in ExAC provided there is no conflicting information BS1

Variant identified in >=2 probands with consistent phenotypes PS4-Supporting

Variant identified in >=6 probands with consistent phenotypes PS4-Moderate

Absent/extremely rare (<0.004%) from large population studies. PM2

Prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls -OR- Variant identified in ≥15 probands with consistent phenotypes PS4

Computational And Predictive Data

A silent variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site -AND- the nucleotide is not highly conserved BP7

Multiple lines of computational evidence suggest no impact on gene or gene product BP4

Multiple lines of computational evidence support a deleterious effect on the gene or gene product PP3

Null Variant in gene with evidence supporting LOF as disease mechanism PVS1-Moderate

Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before PM5

Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants PM4

Same amino acid change as an established pathogenic variant PS1

Functional Data

Functional studies of mammalian knock-in models supportive of no damaging effect on protein function or splicing BS3

Located in a mutational hot spot and/or critical and well-established functional domain. PM1

Functional studies of mammalian knock-in models supportive of a damaging effect on the gene or gene product PS3

Segregation Data

Non-segregation in affected members of a family BS4

Variant segragates in >=3 meioses PP1

Variant segragates in >=5 meioses PP1-Moderate

Variant segregates with >= 7 meioses PP1-Strong

De novo Data

Confirmed de novo without confirmation of paternity PM6

De novo (paternity confirmed) in a patient with disease and no family history PS2

Allelic Data

Observed as comp het (in trans) or double het in genes with overlapping function (e.g. sarcomere genes) without increased disease severity -OR- Observed in cis with a pathogenic variant in any inheritance pattern BP2

Other Data

Variant found in a case with an alternate molecular basis for disease BP5

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.