Fig. 1

Genetic and phenotypic profiles of patients presenting for heritable connective tissue disorders (HCTDs). Flow chart with details for patients who presented to the genetics clinic over a 3.5 year period. Presence of symptoms observed across seven biological systems and next-generation sequencing results for 74 genes included on commercially available connective tissue disorder testing panels were evaluated for 100 unrelated patients. Variants reported as unknown clinical significance (VUS) according to ACMG classifications were further evaluated for potential pathogenicity based on allele frequency, biological conservation, Grantham distance and damaging in silico predictions. Shown are system symptom comparisons for patients with pathogenic (in green) or likely pathogenic (in blue) variants in the same genes as those with potentially pathogenic VUSs (in gray). Reported inheritance patterns are also noted; R = autosomal or X-linked recessive, D = autosomal or X-linked dominant, R/D indicates both autosomal or X-linked recessive and dominant have been reported