When found in a patient confirmed to have disease, novel variants in some genes and regions are empirically shown to have a sufficiently high probability of pathogenicity to support a “likely pathogenic” classification, even without additional segregation or functional data. This could increase the yield of high confidence actionable variants, consistent with the framework and recommendations of current guidelines. The techniques outlined offer a consistent and unbiased approach to variant interpretation for Mendelian disease genetic testing. We propose adaptations to ACMG/AMP guidelines to incorporate such evidence in a quantitative and transparent manner.

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: The case of hypertrophic cardiomyopathy / Walsh R.; Mazzarotto F.; Whiffin N.; Buchan R.; Midwinter W.; Wilk A.; Li N.; Felkin L.; Ingold N.; Govind R.; Ahmad M.; Mazaika E.; Allouba M.; Zhang X.; De Marvao A.; Day S.M.; Ashley E.; Colan S.D.; Michels M.; Pereira A.C.; Jacoby D.; Ho C.Y.; Thomson K.L.; Watkins H.; Barton P.J.R.; Olivotto I.; Cook S.A.; Ware J.S.. - In: GENOME MEDICINE. - ISSN 1756-994X. - ELETTRONICO. - 11:(2019), pp. 0-0. [10.1186/s13073-019-0616-z]

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: The case of hypertrophic cardiomyopathy

Mazzarotto F.;Olivotto I.;
2019

Abstract

When found in a patient confirmed to have disease, novel variants in some genes and regions are empirically shown to have a sufficiently high probability of pathogenicity to support a “likely pathogenic” classification, even without additional segregation or functional data. This could increase the yield of high confidence actionable variants, consistent with the framework and recommendations of current guidelines. The techniques outlined offer a consistent and unbiased approach to variant interpretation for Mendelian disease genetic testing. We propose adaptations to ACMG/AMP guidelines to incorporate such evidence in a quantitative and transparent manner.
2019
11
0
0
Walsh R.; Mazzarotto F.; Whiffin N.; Buchan R.; Midwinter W.; Wilk A.; Li N.; Felkin L.; Ingold N.; Govind R.; Ahmad M.; Mazaika E.; Allouba M.; Zhang X.; De Marvao A.; Day S.M.; Ashley E.; Colan S.D.; Michels M.; Pereira A.C.; Jacoby D.; Ho C.Y.; Thomson K.L.; Watkins H.; Barton P.J.R.; Olivotto I.; Cook S.A.; Ware J.S.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1176338
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