Add Mendelian Association Details

1.

Add one or more diseases or phenotypes as follows.

1. In the Disease/Phenotype field, enter a disease or phenotype.
   As you type, a list of possible matches appears to assist your search. The name of the ontology is displayed in parentheses after the phenotype name.
2. Select an entry from the list or press Enter to accept the first match.
3. To remove an entry, select ×.

2.

Select the Interpretation drop-down arrow, and then select the interpretation:

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Pathogenic—Segregates with disease in multiple unrelated cases with control data. The variant is in a highly conserved region. Functional studies or other evidence indicate a deleterious effect on gene expression.

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Likely Pathogenic—Reported in some case studies with or without control data. The variant is in a highly conserved region. Functional studies or other evidence highly suggest a deleterious effect on gene expression.

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VUS—Nothing about this variant has been reported, or reported information is incomplete or contradictory.

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Likely Benign—Functionally normal. Reported in a few cases with little or no control data. The variant might be nonconserved and predicted to be tolerated. Based on disease prevalence and penetrance information, the variant frequency is higher than expected in the general population.

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Benign—Functionally normal. Reported at high frequency in control data and does not segregate with disease. The variant might be nonconserved and predicted to be tolerated.

3.

Select the Mode of Inheritance drop-down arrow, and then select the mode of inheritance:

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Autosomal Dominant—The gene is on a nonsex chromosome. A single copy of the mutation associated with disease is sufficient to cause the disease.

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Autosomal Recessive—The gene is on a nonsex chromosome. Two copies of an abnormal gene must be present for disease to develop.

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X-Linked Dominant—A dominant gene is on the X chromosome.

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X-Linked Recessive—A mutation in a gene on the X chromosome causes a phenotype to be expressed in males and in females who are homozygous for the gene mutation.

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X-Linked Not Specified—Inheritance of genes on the X chromosome but it is not known if the gene is dominant or recessive.

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Y-Linked—Inheritance of genes on the Y chromosome.

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Complex—Two heterogenous recessive alleles are present at a locus that can cause disease.

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Inconclusive—The inheritance cannot be determined.

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Mitochondrial—A mutation in mitochondrial DNA.

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Unknown—The mode of inheritance is not known.

4.

Select the Confidence drop-down arrow, and then select a confidence level.

5.

[Optional] Enter a penetrance ratio in the Penetrance field.

6.

[Optional] Enter a brief description in the Curator Summary field.

7.

[Optional] Add evidence. See Adding Evidence.

8.

Select Save.

The association is submitted for approval and is listed with a status of In Progress.