PatientID: 31

KindredID: 31

Case: F, 42Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

CaseHPOFreeText: CNS hemangioblastoma. Other phenotypes presented but not specified (one or more of: pancreatic cyst or tumor, renal or hepatic cyst). Diagnosed with VHL Type 1.

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128P (c.383T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 1208816, https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L128P (c.383T>C)

MultipleGeneVariants: N/A

PatientID: 30

KindredID: 30

Case: F, 27Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

CaseHPOFreeText: CNS hemangioblastoma. Other phenotypes presented but not specified (one or more of: pancreatic cyst or tumor, renal or hepatic cyst). Diagnosed with VHL Type 1. Phenotypes revised from previous reports (see “PreviouslyPublished” section below for PMID).

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19270817

SupplementalData: N/A

Variant: p.L128P (c.383T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 1208816, https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L128P (c.383T>C)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 5

Case: F, 27Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: None. Sporadic

CasePresentingHPOs: HP:0010797; HP:0005584 (hemangioblastoma, renal cell carcinoma)

CaseHPOFreeText: 'Other' phenotypes found in patient. These are noted in the paper to include: pancreatic neuroendocrine tumors (PNETs), renal and pancreatic cysts and central nervous system tumors, although it is not clearly stated that patient has all. (See Table 1).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128P (c.383T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 1208816 https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: L128P (c.383T>C)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: F, 11Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Her cousin (case 2) underwent a bilateral adrenalectomy and had the same VHL mutation.

CasePresentingHPOs: HP:0006748, HP:0002865 (Adrenal pheochromocytoma, Medullary thyroid carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584, HP:0010797 (renal cell carcinoma, hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128F (c.382C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 496060 https://www.ncbi.nlm.nih.gov/clinvar/variation/496060/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L128F (c.382C>T)

MultipleGeneVariants: N/A

PatientID: 3

KindredID: 3

Case: F, 41Y0M, Ethnicity Unknown

DiseaseAssertion: hemangioblastoma

FamilyInfo: Positive family history of VHL disease.

CasePresentingHPOs: HP:0006766; HP:0006770; HP:0010797 (papillary renal cell carcinoma, clear cell renal cell carcinoma, hemangioblastoma)

CaseHPOFreeText: multiple cystic, bilateral renal cysts and partial nephrectomies with tumor enucleations were performed (6 tumors total that ranged from 0.4-6.5cm); Fuhrman nuclear grade 2: identified as clear cell papillary in 2 of them, and clear cell carcinoma in 4.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128P (c.383T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 1208816 https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816/

CAID: N/A

gnomAD: N/A

VariantEvidence: diffuse staining with cytokeratin 7 (CK7) was positive + and CD10 + (rare). P504S was negative -.

MutationType: missense_variant;transition

CivicName: L128P (c.383T>C)

MultipleGeneVariants: N/A

PatientID: 24

KindredID: 3775

Case: F, 39Y3M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

CaseHPOFreeText: She presented with 1 radiographic pancreatic neuroendocrine tumor diagnosed at age 38Y. Follow up 15M after EN surgery, currently no evidence of disease.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128F (c.381_382delinsTT)

LegacyVariant: p.L>F (c.594_595GC>TT)

CaseProblemVariantFreeText: N/A

ClinVarID: 223203 https://www.ncbi.nlm.nih.gov/clinvar/variation/223203

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: delins

CivicName: L128F (c.381_382delinsTT)

MultipleGeneVariants: N/A

GroupID/ KindredID: F41

Case: Sex unknown, 22Y0M, Spanish

DiseaseAssertion: assumed VHL

FamilyInfo: familial antecedents found; unknown of any additional features to index case relatives

CasePresentingHPOs: HP:0009711; HP:0006770; HP:0006880; HP:0000107; HP:0001737 (retinal capillary hemangioma, clear cell renal cell carcinoma, cerebellar hemangioblastoma, renal cysts, pancreatic cysts)

CaseHPOFreeText: Multiple lesions were found with the patient’s cerebellar hemangioma. Unilateral ccRCC. Age of onset is 22Y0M.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128R (c.383T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753891 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.383T%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: L128R (c.383T>G)

MultipleGeneVariants: N/A

PMID 30291432

MONDO MONDO:0800183

Notes minigene splicing assay for c.-128-2del that shows majority of transcript is one where exon 3 is skipped with some but greatly reduced canonical transcript levels

PMID 28321846

Gene: PAX6

Variant NM_001368894.2:c.-128-2del

Disease: Ocular dysgenesis

InheritancePattern: AD

Disease PAX6-related ocular dysgenesis MONDO:0800183

Proband 26.03 and apparently de novo

GroupID: 4783

DiseaseAssertion: VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Each group represents a family.

GroupPresentingHPOs: HP:0002666; HP:0009711; HP:0030405 (Pheochromocytoma, Retinal capillary hemangioma, Pancreatic endocrine tumor)

GroupHPOFreeText: 3/3 members with pheochromocytoma, 1/3 members with retinal angioma, Diagnosed as a VHL Type 2B family. Localized pancreatic neuroendocrine tumor is also associated with this family but the number of family members affected is not specified.

GroupNotHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

GroupNotHPOFreeText: No CNS hemangioblastoma, RCC or cyst presentations.

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128F (c.382C>T)

LegacyVariant: c.595C>T

CaseProblemVariantFreeText: N/A

ClinVarID: 496060, https://www.ncbi.nlm.nih.gov/clinvar/variation/496060/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant reported as 595, C to T (Leu to Phe), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.382C>T, p.Leu128Phe (NM_000551.3).

MutationType: missense_variant;transition

CivicName: L128F (c.382C>T)

MultipleGeneVariants: N/A

PMID: 18241071

Gene: PAX6

Variant NM_001368894.2:c.-128-2del

Disease: Ocular dysgenesis

InheritancePattern: AD

Disease PAX6-related ocular dysgenesis MONDO:0800183

PMID: 9536098

Gene: PAX6

Variant NM_001368894.2:c.-128-2del

Disease: Ocular dysgenesis

InheritancePattern: AD

Disease PAX6-related ocular dysgenesis MONDO:0800183

GroupID: 8

Case: Age, Sex, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 1 individual belonging to 1 family was mentioned with this VHL mutation. No other family info was provided.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Other manifestations aside from pheochromocytoma are possible; but not specified.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128F (c.381_382delinsTT)

CaseProblemVariantFreeText: Paper called "L" Lysine but it matches to Leucine in all 3 cases. Likely an error in word choice by authors.

LegacyVariant: N/A

ClinVarID: 223203 https://www.ncbi.nlm.nih.gov/clinvar/variation/223203

CAID: CA357088 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.381_382delinsTT

gnomAD: N/A

VariantEvidence: N/A

MutationType: delins

CivicName: L128F (c.381_382delinsTT)

MultipleGeneVariants: N/A

From this it is suggested that it is important to know Latin and Greek as a scholar in those times due to the large volumes of books that are still written in those languages and yet to be translated. It shows that in order to continue an education in the field of science one must also be able to understand the "language of science" which is often not English.

Eric Yu

Manufacture and commerce is mentioned here. Today when we speak about college education these two are probably normal in conversation of a student studying things like business or engineering. Take note that agriculture is mentioned as well. It is not only mentioned but the first mentioned. This suggests that a lot more emphasis is put on agriculture by the society at the time and thus the importance of including it in higher education.

Eric Yu

In my ethical engagement, which is centered on the interpretations of the New Testament, my professor is well-versed in the book and the religion itself; however, she does an incredible job at teaching the class and leading discussions in an unbiased way. She does not impart her views on the religion -- because the University is public and strives to “place all sects of religion on an equal footing” (although this is not always carried out successfully). In my experience, I think that the University has consistently adhered to this section of the text.

It is interesting that specific qualifications and are not stated, because it makes it more difficult to compare the intellectual capacity of admitted students to the University when it was first founded and current applicants and admitted students. It mentions the “circle of attendance” which implies the emphasis placed on the organization of the University to maximize the students’ presence in each of their classes. This humorously foreshadows the phenomenon of “skipping classes” in college, whether intended or not, by meticulously scheduling lectures (especially in the context of the University’s size and layout at the time) to anticipate the problem.

Similarly to the architecture and military courses, Chemistry is mixed along with the theory of Agriculture in order to promote practicality and applicability. Modern-Day chemistry teaches the basics of the atomic structure, simple compounds, and nomenclature. However, their definition of chemistry is heavily tied to the theory of Agriculture. Similarly to the military and architectural courses, chemistry courses are taught in order to support the health and wellbeing of US citizens. Such courses will allow students to better improve the living conditions of the United States. It is odd for the report to explicitly differentiate Mineralogy from Geology especially during their time of age. It can assume that Mineralogy was studied to research helpful minerals that would improve weaponry, alternative raw materials, and agriculture. As for ideology, it could be assumed that ideology was taught in order to share the ethics of UVA. This can be implied based on the UVA’s strict honor policy and how it teaches students the harsh punishment that could come from acts of dishonesty and disrespect.

Architecture and Military are taught hand-in-hand in order to strengthen the military of the United States. Ever since the Revolutionary War and their received freedom from the oppressive British monarchies, the courses taught at the University of Virginia during the 19th century were more practical and applicable that would better support the powerhouse of the United States and its citizens. Those they named it as “art,” the Fortification course further supports the reason as to why Architecture and Fortification/Military goes together since it support the military strength of the United States and UVA. It is understandable to see how housing is not discussed in the courses. Upon experiencing the traumatic Revolutionary War, the protection and fortification of the country became first priority compared to ordinary interior designing and housing.

I enjoy this part of the report because it displays how UVA really is an institution that is tied to the ideas of the past. It also shows how thinking was different then compared to now. First it ties the learning and teaching of the time to the ancient classics. Up until about this time most of the ideas in the world came from this time period a long time ago. It is around the time this document was made that learning started to shift to focus on the newer discoveries rather than relying on the old philosophers.

I love this section of the report because it highlights the differences between then and today. Before, There was a clear need for people to be taught how to protect the country. At this point the nation was still new and there was a need for forts to protect the country from invasion. While it still may be important for people to know how to build forts today, it is not nearly as critical as it was for them in that time period.

It is amazing how many services they wanted to cram into one building but I guess back then it would have been seen as more efficient to put the examination room in the same multipurpose building. I also appreciate the freedom of religion aspect of the worship clause and how there is absolutely no bias towards the worship of any particular religion or sect of Christianity which was probably common at other universities of the time.

It makes sense how important Jefferson believed writing was as he was a part of the team who wrote the first draft of the deceleration or independence and experienced the writing of the constitution first hand. He saw that writing was a key part in forming a country and knew it was essential that his students learn the skill in order to change the world.

It is great that it is mentioned here the confirmed psychological study that ability to study language declines drastically over time

This statement evoked some further thinking in me. I realized that United States at this time is a new country and this very quote implies it so. It says that German is a language that needs to be learned in order to learn from the most advanced knowledge from science and some other subjects. United States is still developing and learning from stronger and more advanced countries.

Why was the central college already in Albermarle? I found online receipts of tax payments on the lands and slave laborers of the Central college. I also found Jefferson's bill calling for the creation of the Central college. Why did the central college come first? Why did Jefferson create the central college instead of just establishing a state university?

I find this line very interesting. It is stated that reading can improve your morals and faculties; while the latter is obviously true, the idea that reading can improve your morals is debatable. Reading more does not make someone a better person. Reading can make you more open to other ideas, which can be a very good thing, but this implies that reading can improve your morals, which is an odd statement. I wonder what books they would have considered to improve morals, and what books didn't make the cut. Actually, even more so, I wonder what kind of "morals" were being striven for.

I find it very interesting that in this context, chemistry is only used to comprehend the theory of agriculture. It seems odd that, even though chemistry has so much more to offer and explore (such as Dalton's atomic theory in the beginning of the 1800s), Agriculture is the only thing mentioned. This was a time when there was so much about to be discovered but that seems to not be acknowledged even if UVA was to be a great place of education.

Hearing Jefferson discuss the potential to create a “new man…into qualities of virtue and social worth,” despite whatever “wild & uncultivated tree” he might originally appear to be, reminds me of his contrasting words from Notes on the State of Virginia (1785). In the context of contrasting the natural state of white men and black, he states, “…the difference is fixed in nature…and this difference is of no importance? Is it not the foundation of a greater or less share of beauty in the two races?” and then later, “It is not their condition, then, but nature, which has produced the distinction” (Query 14). Though Jefferson claims to firmly believe that no man is fixed in his state of being, it cannot be overlooked that Jefferson’s belief was qualified by his own words. Though he is remembered as a believer in the potential “social worth” of each individual, he always fell short in grasping this idea completely; he never reached beyond the thinking that this was not the case for “those of colour.”

The only pronoun in this is "he". This stresses how Jefferson and UVA had a college only In mind for men. I also was shocked at the "preserve" his ideas. I believe a huge part of college is not to preserve but to expand, get uncomfortable and learn about new things. I wonder why a person of Jeffersons intellect wouldn't encourage others to expand their ideas rather than preserve.

I find this very interesting, but not surprising given the time period. This mentions how it was chosen based off of convenience to white people to get an education closer to them. I'm curious if this pertained to white women as well, because they are "white" but during this time most women weren't going to college. It's also interesting to see this school's more conservative roots, something that gets forgotten today. This expresses the white male dominance during this time, a southern conservative value that today really isn't shown at UVA.

This phrase, especially the way it stands out on its own in this document, shows the emphasis that the founders of UVA wanted to have on entrepreneurship and the independence of its students during and after their time at the university. That being said, it's interesting that there aren't any explicit business classes or ones relating to economics (except for political economy). Most classes seem to point not toward individual businesses but more toward collaborative ones.

This line in particular relates to the provided document in resources, "A Bill for Establishing Religious Freedom." That bill states "That to compel a man to furnish contributions of money for the propagation of opinions which he disbelieves and abhors, is sinful and tyrannical; that even the forcing him to support this or that teacher of his own religious persuasion, is depriving him of the comfortable liberty of giving his contributions to the particular pastor whose morals he would make his pattern, and whose powers he feels most persuasive to righteousness [...]" This discusses how wrong it is to force a religion onto others and it seems in The Rockfish Gap report that UVA was founded with the same principles in mind. I find the seemingly progressive and accepting view towards religion shocking in comparison to the clear racism throughout this report. Considering this, it seems clear that they aren't really in support of all religions but rather those associated with white people. I think what they really meant by "freedom of religion" is the freedom to choose between the different types of Christianity. However, Thomas Jefferson was a huge supporter of separating the church and state so maybe he was more accepting of other religions than I am giving him credit for.

Although it was stated earlier on, at the beginning of the paragraph that there were doubts regarding the university and whether education should really be encouraged, especially in the sciences and arts, similar to arguments made by Jean-Jacques Rousseau. However, the founders of the University were evidently of the opinion of the importance of public education for students in multiple areas of study, rather than just what their fathers were to teach them. Without as many people of this opinion in support of the foundation of the University it would have been more difficult to set up and once set up, possibly not as easy to keep running. Another point to notice is the reference to "indigenous neighbors" which, along with the following sentence, also shows the negative opinion of thee white male founders towards Native Americans.

Right off the bat in only the third paragraph of the report there is this statement that narrows down the scope of professors to a single gender, male, by saying "his" family. Of course this is not really anything unusual during the time period, however, it's still quite noticeable how it is just assumed that the professors, and they do the same with students later in the document, will all be male. Today anything like this would be outrageous at a public university such as our University of Virginia.

I am questioning why Astronomy was determined to be one of the founding branches of study. Chemistry was studied in relation to its uses in agriculture, but what was astronomy practical for at this time? Wikipedia says that the analysis of elements in the sun, spectroscopy, was first done in 1814. link to wikipedia

It's very interesting how the writers of this document see dancing, music, and drawing as hobbies that solely "furnish amusement and happiness" except when drawing is used for military use. They believe this so much so, in fact, that they will not even provide courses or professors for the arts, but only "proper apartments" in order to practice art. Further, they wanted to make the students pay an additional amount and find their own teachers in order to participate in the arts. Why would they build additional buildings for the arts but yet not provide any resources for further study of them?