Supplementary Table S1. Variation Found in 56 ACMG Genes in Whole Exome Sequences of 232

Supplementary Table S1. Variation found in 56 ACMG genes in whole exome sequences of 232 individuals.

Whole exome sequences from 232 individuals representing 89 families were analyzed for rare (MAF0.01), nonsynonymous and splice variants and indels in the 56 genes on the ACMG list.1 We identified 249 distinct variants, some of which were seen in more than one individual. The number and density of variants (number of variants/kb coding sequence) varied by gene. Some genes had better sequencing coverage than others.

Supplementary Table S2. Discordant classification of variants among databases.

Three databases (HGMD,2,3 ClinVar,4,5 and Emory6,7) were examined for classification of the 249 distinct variants identified in 232 individuals’ whole exome sequences. Of 48 variants which were classified by more than one database, 22 variants were given discordant classifications between databases. We then compared these database classifications to our variant classifications derived from the Dorschner et al. method8 and found that variant classifications given by the ClinVar and Emory databases but not HGMD were generally consistent with our variant classifications. These results show the lack of consensus for variant classification methodologies among currently available databases. (Abbreviations: DM-Disease-causing (pathological) mutation, based on information from the literature; VUS-Variant of Uncertain Significance; N/A- variant was not listed in this database).

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