 All right, good morning. Great setup, how often at a scientific meeting do you get to hear golly gee willikers? So, similar to Sharon, I just want to start. We had another similar case to the VHL case she mentioned, and maybe it's a Philadelphia thing, but this was a many year case with an individual who had subtle features of VHL who had a genetic diagnosis that was thought to be pathogenic, had gone through many years of decisions about pregnancies and terminations later to find out that it was a benign variant. So, I think the repercussions of this are huge for the individual, and we do need better guidelines. So, having said that, I'm going to counter Sharon's argument that we should be more limiting and say that we should be more expansive especially when it comes to pediatrics. So, these are some of the comments I extracted from the 2013 paper with the 56 genes. This is meant to be a minimum list of must report, and the conditions for the vast majority are autosomal dominant. They're really primarily adult or later onset disorders with only three being specifically pediatric. Many of the 17 childhood adult overlap are really leaning more towards adult and not very specifically towards pediatrics. Another statement, we have a fiduciary duty to prevent harm, supersedes concerns about autonomy. Autonomy is preserved as patients have the right to decline clinical sequencing, which is great, but a little complicated from a pediatric perspective where they don't have a real option and you're putting that on parental choice. The ethical concerns about providing genetic risk about adult onset diseases were outweighed by the potential benefit to the future health of the child and parents. And I think, again, I'm not really going to talk about a lot of the LC issues, and that's been published quite a bit and discussed a little bit here, but the things we have to think about a little bit closer. And then incidental variants should be reported regardless of age of the patient. And finally, conditions that are part of other screening modalities such as the newborn metabolic screening were pretty much excluded from this list, and I think that has a big impact on what we do in pediatrics. So between the 2014 update and 2016 new list, there's the opt-out option that was added. They removed milk, as you heard, and they added the other genes, which Wendy went through. And it's just nice to have at least another recessive gene added to the list that's relevant and a metabolic gene, another recessive or X-linked gene, but has an impact for the female carriers, as you've heard. So I'll say, first of all, it's been said over and over again, children are not little adults for the most part. And some of the differences that we face is that clinical manifestations really vary by age where there are severe disorders that may not manifest when the child's being screened, not just as a late onset cancer, but a severe metabolic condition, for example, that you can intervene with. And we've seen over and over that many sick children may not manifest a secondary diagnosis that can have a significant impact on their care because it's masked by the primary diagnosis. There are issues of consent and autonomy that need to be more carefully considered when returning secondary findings for late or adult onset disorders, both for the child and for potentially the affected parent. And there may be alternate pathways to returning results to parents secondary findings that may not have to be returned to the child or at least have an option for that child to make that decision once their adults are able to consent. And then just looming on the horizon, obviously, which we don't talk about that often in this setting, is the impact of these on prenatal diagnostics, which is increasing where you really have much less phenotypic data. And then as we expand going forward, that inevitability of healthy individuals and children using the screening may also change the type of incidental findings we report back. So just to, I just put the slide in to say this isn't something new, obviously. We've been dealing with this since we've been doing single gene screening, since we've been doing chromosomal microarrays. This has been the experience at CHOP. So for a test for which there is no informed consent at most institutions, the microarrays, we have an almost 2% incidence of secondary findings that we deem important enough to report back. And here's the breakdown, 22% are mostly one-offs, but there are some genes in some common categories that we feel are important to return, and many of these are not on the ACMG recommendation list. And as we're moving forward, and exomes and genomes are going to start to report copy number back as well, we have to be cognizant of this. So at CHOP, we've sort of expanded, and we don't have too much time, but we've kind of expanded our categorization of the type of things that we will return. And they echo some of the ACMG guidelines but are a little more expansive, but really just to state that we have an expanded list that we do return at CHOP. Here are some early examples of cases that just sort of underscore some of the issues we brought up. The first patient on your left was a child who presented with failure to thrive, reflux, some developmental-delayed dysmorphic features, also had some seizures and short stature that continued. And there was a clinical suspicion for floating harbor, which was confirmed by a DeNovo SCRAP mutation, but it was also found to have compound heterozygous, known pathogenic mutations in the ASL gene that relates to Arginosuccinic aciduria, and that nicely can be confirmed biochemically was not picked up on a newborn screen and impacted his care and treatment and outcome. Again, something that's not on the ACMG-59 gene list. The other child was an international patient from consanguinous parents, presented with developmental delay, hypotonia, some ongoing motor delays as she got a little older, and she was found to have a pathogenic mutation or a homozygous pathogenic mutation, the FKRP, related to limb girdle muscular dystrophy, but also was found to have homozygous pathogenic mutations in ACAT-L, cause of long chain acyl-CoA dehydrogenase deficiency that probably impacted her phenotype, but would not have been. Both of these kids, if they had targeted testing, would not have been identified to have these, but I think was important to return, and both of which have treatments that can improve outcomes. So, the overall CHOP clinical experience is that we had about 14 of 347 exomes for a 4% rate that had an incidental finding. Only 43 of the broader population, 390, declined to receive secondary findings. And these mutations, for the most part, were in the ACMG gene list, two of which were not, though, one of which were compound heterozygous known pathogenic mutations in CFTR, the other was an NR3C2 mutation related to pseudo-hypoaldosterism, again, a treatment for that. So, in the PD-Seq experience, this is sort of our, and for our PD-Seq project, we expanded the incidental finding list because we wanted almost everyone to have an incidental finding because part of our study was to really see how return of incidental findings impacted the families and the clinicians who had to deal with them, but so everyone got the immediately medically-actionable results had to be returned, and then there was choices for medically-actionable childhood and adult onset and carrier status. So, the results from our cohort to date is that basically only about 5% opted out of secondary findings. The majority of results that we were returning, so of the 105 that we returned, 74% were pathogenic, 26% likely pathogenic, 78 of those 105 were new variants that were deemed to be pathogenic or likely pathogenic, but not reported. 62 patients received these secondary findings with an average of about 1.7 secondary findings per patient. The vast majority of those, again, were carrier status. Six of the 105 were immediately medically-actionable, only one of which was not on the ACMG gene list, which was an RHO gene mutation associated with night blindness and retinal abnormalities, and one was a medically-actionable adult onset mutation, a BRCA1 pathogenic variant. So, even expanding it to this broad number, although there are some different analysis issues, it really doesn't result in significant increasing in reporting, except for those rare cases that I told you about. But just last week in clinic, we returned this result, this PDC result, which, again, I think underscores some of the differences in pediatrics. So, this was a child first seen at two months old. Here he is pictured here for bilateral sensory neural hearing loss. Otherwise, no real medical history was elicited. He had dystopia canthorum, as you can see on the picture. So, we were a little suspicious for Wardenburg. Insurance allowed us to do a microarray and do the Wardenburg syndrome testing, which were both normal and large-scale panel and exome was denied and they were enrolled in PDC and had a number of VUSs related to primary finding. We think the TMC1 compound heterozygous mutations, although their VUSs are the likely answer, given the severity of the hearing loss in this child. The father had a mild hearing loss. The father's mother had a mild hearing loss of the MYH9, thought might be a possibility, but it has a more severe hearing loss. So, we really think the TMC1 is the answer, although we did have a secondary finding of sucrose isomaltase compound heterozygous mutations and they're the two most common mutations seen in sucrose isomaltase deficiency and we return those results to the family and the child's now two years of age and when we return the results to the family, they said, oh, that explains everything and the child has a history of loose stools and diarrhea, poor weight gain for which he's been followed, would never have had this diagnosis specifically made but is being referred to GI and again, there's treatment for this and they have another child since his child was enrolled who does not have those features so we have a nice control in the family to see and sucrose isomaltase is a little complicated because you have a spectrum from normal to very severely affected kids. So, we at CHOP and through PDC have sort of expanded our secondary finding list to be inclusive of this. This just shows you we work with our champions, people in all different specialties across CHOP to say what genes should be on a secondary finding list. This just highlights the metabolism genes and the ones with asterisks are those that are picked up on newborn screening, the ones in red are ones that are often missed and those without asterisks, mostly the lysosomal storage disease and glycogen storage diseases are not picked up so there are many genes that would not be picked up on newborn screens or would be missed. So in summary, I would say that recessive and hemizygous conditions need to be included on secondary gene list and pediatrics and there's a slight movement towards that on the new update. There's not, it's not enough to assume that they'll be picked up on newborn screening so many are not, like I mentioned, LSDs. Some can be missed like MCAD most notably and we see a growing number of populations, international patients and patients from outside the United States who do not have newborn screening so to eliminate those possibilities, I think is not correct. We need more frequent updating of the list, we need pediatrics specific list recommendations more likely than just one unified list and we start to have to think about prenatal and healthy children as well in this. Thank you.