Abstract: Provided are methods and systems for determining the clinical significance of a genetic variant. The methods entail determining, for the variant, (a) a function score based on known impact of the variant on a biological function of a cell or protein, (b) a frequency score based on the frequency of the variant in a population, (c) a co-occurrence score based on how the variant co-occurs with a reference variant having known clinical significance relating to a clinical disease or condition, and (d) a family segregation score based on how the variant segregates with a disease or condition in a family; and aggregating, on a computer, the function score, the frequency score, the co-occurrence score, the family segregation score to generate a clinical significance score indicating the clinical significance of the genetic variant.

Abstract: Provided are methods and systems for determining the clinical significance of a genetic variant. The methods entail determining, for the variant, (a) a function score based on known impact of the variant on a biological function of a cell or protein, (b) a frequency score based on the frequency of the variant in a population, (c) a co-occurrence score based on how the variant co-occurs with a reference variant having known clinical significance relating to a clinical disease or condition, and (d) a family segregation score based on how the variant segregates with a disease or condition in a family; and aggregating, on a computer, the function score, the frequency score, the co-occurrence score, the family segregation score to generate a clinical significance score indicating the clinical significance of the genetic variant.

Abstract: Provided are methods and systems for determining the clinical significance of a genetic variant. The methods entail determining, for the variant, (a) a function score based on known impact of the variant on a biological function of a cell or protein, (b) a frequency score based on the frequency of the variant in a population, (c) a co-occurrence score based on how the variant co-occurs with a reference variant having known clinical significance relating to a clinical disease or condition, and (d) a family segregation score based on how the variant segregates with a disease or condition in a family; and aggregating, on a computer, the function score, the frequency score, the co-occurrence score, the family segregation score to generate a clinical significance score indicating the clinical significance of the genetic variant.

Abstract: Provided are methods and systems for determining the clinical significance of a genetic variant. The methods entail determining, for the variant, (a) a function score based on known impact of the variant on a biological function of a cell or protein, (b) a frequency score based on the frequency of the variant in a population, (c) a co-occurrence score based on how the variant co-occurs with a reference variant having known clinical significance relating to a clinical disease or condition, and (d) a family segregation score based on how the variant segregates with a disease or condition in a family; and aggregating, on a computer, the function score, the frequency score, the co-occurrence score, the family segregation score to generate a clinical significance score indicating the clinical significance of the genetic variant.

Abstract: Methods of identifying polymorphisms associated with hereditary spastic paraplegia (SPG), are described. The polymorphisms associated with SPG include specific mutations in the receptor expression enhancing protein 1 (REEP1) gene. Also described are methods of diagnosis of SPG.

Abstract: Methods of identifying polymorphisms associated with hereditary spastic paraplegia (SPG), are described. The polymorphisms associated with SPG include specific mutations in the receptor expression enhancing protein 1 (REEP1) gene. Also described are methods of diagnosis of SPG.

Abstract: Methods of identifying polymorphisms associated with ataxia-ocular apraxia 2 (AOA2), are described. The polymorphisms associated with AOA2 include specific mutations in the senataxin (SETX) gene. Also described are methods of diagnosis of AOA2, as well as methods of assessing an individual for carrier status for AOA2.