PatientID: 4

KindredID: 4

Case: M, 50Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: 55 patients treated at Asan Medical Center in Korea treated between January 1995 and February 2013 clinically diagnosed with VHL disease and presenting with pancreatic lesions.

CasePresentingHPOs: HP:0001737 (pancreatic cysts)

CaseHPOFreeText: At age 45, the patient presented with a cystadenoma. It was radiologically diagnosed as a mucinous cystadenoma but pathology revealed serous cystadenoma. The patient was followed up 59.5 months later.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S111R (c.331A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351751320 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.331A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName:S111R (c.331A>C)

MultipleGeneVariants: N/A

PatientID: 177

KindredID: 69

Case: F, 53Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The male proband, patient 143, was diagnosed with renal cell carcinoma and multiple pancreatic cysts/tumors at age 33. His mother, who was not confirmed with the mutation, had a CNS hemangioblastoma at 30, retinal angioma at 54, and renal cell carcinoma at 50. His sister had a CNS hemangioblastoma at 28, and renal cell carcinoma/ multiple pancreatic cysts/tumors at 35. His niece, who was not confirmed with the mutation, had a CNS hemangioblastoma at age 12. His aunt had a CNS hemangioblastoma at 37, retinal angioma at 45, and renal cell carcinoma at 53. The son of his aunt was asymptomatic at the time of analysis.

CasePresentingHPOs: HP:0010797; HP:0009711; HP:0005584 (Hemangioblastoma, Retinal capillary hemangioma, Renal cell carcinoma)

CaseHPOFreeText: The proband's aunt presented with a CNS hemangioblastoma at age 37, retinal angioma at age 45, and renal cell carcinoma at age 53.

CaseNotHPOs: HP:0002666; HP:0001737; HP:0001732 (Pheochromocytoma, Pancreatic cysts, Abnormality of the pancreas)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.C162W (c.486C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223227; https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 45Y0M, Ethnicity Unknown

DiseaseAssertion: Clear Cell Renal Cell Carcinoma

FamilyInfo: N/A

CohortInfo: The National Cancer Institute has a frozen tumour bank of ccRCC tumours that have been removed from VHL patients. We selected six patients, three males and three females, with at least five tumours from a single surgery from one kidney.

CasePresentingHPOs: HP:0006770 (clear cell renal cell carcinoma)

CaseHPOFreeText: One of the samples from this patient had few variants and clustered with the normal samples. Further inspection showed these samples were cyst-like rather than tumours, so they were excluded from further analysis. This suggests that the patient had renal cysts alongside ccRCC at age 45.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R176fsGfs*26 (c.526del)

LegacyVariant:N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 625257 https://www.ncbi.nlm.nih.gov/clinvar/variation/625257/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName:R176fs (c.526del)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 1

Case: Sex Unknown, 55Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Significant family history. Pedigree follows 8 generations (see Figure 3). Family immigrated to Iowa, US, from Baden-Baden, Germany, in 1832; Likely sharing a common ancestor to the traced lineage of the Black Forest region of Germany.

CasePresentingHPOs: HP:0002666; HP:0009711 (pheochromocytoma; retinal capillary hemangioma)

CaseHPOFreeText: 45Y at first pheochromocytoma and ocular angioma (retinal capillary hemangioma).

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98H (c.292T>C)

LegacyVariant: p.Y98H (c.505T>C)

CaseProblemVariantFreeText: N/A

ClinVar: 2223 https://www.ncbi.nlm.nih.gov/clinvar/variation/2223/

CAID: N/A

gnomAD: 0.00001343 https://gnomad.broadinstitute.org/variant/3-10183823-T-C

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Y98H (c.292T>C)

MultipleGeneVariants: N/A

GroupID: 39

Case: 45Y0M, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 1 of the 573 patients discussed in this paper were found to have this variant. This mutation was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0009711; HP:0006880; HP:0005584 (retinal capillary hemangioma; cerebellar hemangioblastoma; renal cell carcinoma)

CaseHPOFreeText: patient had retinal capillary hemangioma diagnosed at 45Y, cerebellar hemangioblastomas diagnosed at 24Y, and RCC at 45Y

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.K196Rfs*59 (c.584_585delAG) 

LegacyVariant: N/A

CaseProblemVariantFreeText: This mutation also automaps to NM_000551.3:c.585_586delGA

ClinVarID: 547831 https://www.ncbi.nlm.nih.gov/clinvar/variation/547831/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_2_frameshift_variant

CivicName: K196fs (c.584_585delAG)

MultipleGeneVariants: N/A

GroupID: 27

Case: 45Y0M, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 1 of the 573 patients discussed in this paper were found to have this variant. This mutation was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0006880; HP:0005584 (cerebellar hemangioblastoma; renal cell carcinoma)

CaseHPOFreeText: patient had cerebellar hemangioblastoma diagnosed at 25Y, and RCC diagnosed at 45Y

CaseNotHPOs: HP:0009711; HP:0002666 (retinal capillary hemangioma; pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.Q145* (c.433C>T) 

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 625249 https://www.ncbi.nlm.nih.gov/clinvar/variation/625249/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Q145* (c.433C>T) 

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 45Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0006748, HP:0100827, HP:0001894, HP:0009713, HP:0031496 (Adrenal pheochromocytoma, lymphocytosis, thrombocytosis, spinal hemangioblastoma, mucinous cystic neoplasm of the pancreas)

CaseHPOFreeText: At age 45 the patient was admitted for 2-week history of fatigue and muscle weekness. MRI showed bilateral chronic infarcts resulting from multiple cryptogenic strokes in his past medical history. Blood tests revealed unexplained lymphocytosis and thrombocytosis.The patient was found to have bilateral adrenal phoechromocytomas, hemangioblastomas in the spinal cord at T11 and in the cauda equina at L2, and multiple intraductal papillary mucinous neoplasms.

CaseNotHPOs: HP:0005584, HP:0030405 (renal cell carcinoma, pancreatic endocrine tumour)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98H (c.292T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2223 https://www.ncbi.nlm.nih.gov/clinvar/variation/2223/

CAID: N/A

gnomAD: 0.00001343 https://gnomad.broadinstitute.org/variant/3-10183823-T-C

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Y98H (c.292T>C)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 45Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient’s daughter, age 27, presented with two right renal masses and several pancreatic cysts at 22Y. The patient’s brother, age 38, presented with unilateral ccRCC. Both the patient’s daughter and brother were found to carry the mutation the patient carried.

CasePresentingHPOs: HP:0006770; HP:0001737 (Clear cell renal cell carcinoma, pancreatic cysts)

CaseHPOFreeText: The patient presented with right ccRCC and pancreatic cysts.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: SDHB, SDHC, SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: None(c.-77_-32del)

LegacyVariant: N/A

CaseProblemVariantFreeText: The mutation was a deletion in the VHL 5’ UTR, including the promoter.

ClinVarID: 433541, http://www.ncbi.nlm.nih.gov/clinvar/variation/433541

gnomAD: N/A

VariantEvidence: N/A

MutationType: 5_prime_UTR_variant

CivicName: c.-77_-32del

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: 23Y0M, Sex Unknown, Argentinian

DiseaseAssertion: VHL

FamilyInfo: Thus far, it has not been possible to study the parents or close relatives of this patient.

CasePresentingHPOs: HP:0009711; HP:0000107 (retinal capillary hemangioma; renal cyst)

CaseHPOFreeText: Aged 22Y at diagnosis (genetic testing); fulfils type 1 VHL clinical diagnosis. Bilateral retinal hemangioblastomas diagnosed at 22Y, and renal cysts were diagnosed at 23Y (See Table 1 & 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q132Hfs*45 (c.343_395dup)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2497030272 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2497030272

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_2_frameshift_variant; duplication

CivicName: Q132Hfs*45 (c.343_395dup)

MultipleGeneVariants: N/A

PatientID: II:1

KindredID: 1

Case: M, 49Y0M, Spanish

DiseaseAssertion: pheochromocytoma

FamilyInfo: Spanish family of 15 members studied, over 2 generations. 6 members had VHL presentations, 1 was a carrier, and 4 others had the mutation, while 2 were not sequenced. This patient’s 3 children showed VHL phenotypes, and his sister and 2 nieces presented with the VHL mutation.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: first studied at 45Y, the patient had bilateral accumulation of pheo tumors, right: 9cm and left: 2cm

CaseNotHPOs: HP:0006880; HP:0009711 (cerebellar hemangioblastoma, retinal capillary hemangioma)

CaseNotHPOFreeText: Brain MRI and CT-scans were normal, and no signs of retinal angiomas were present.

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167W (c.499C>T)

LegacyVariant: p.R238T, C>T

CaseProblemVariantFreeText: N/A

ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

CAID: N/A

gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

PatientID: 4

KindredID: 3

Case: M, 45Y0M, Arab

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL disease was described for this patient. Immediate family members were recommended to genetically test for the relevant variant or monitor for VHL-related symptoms.

CasePresentingHPOs: HP:0006880; HP:0009713; HP:0000107; HP:0001737; HP:0000787 (cerebellar hemangioblastoma; spinal hemangioblastoma; renal cyst; pancreatic cysts; nephrolithiasis)

CaseHPOFreeText: At 40Y, Patient 4 was diagnosed with spinal and cerebellar hemangioblastomas, as well as multiple renal and pancreatic cysts. He was diagnosed with VHL disease type 1. At 43Y, renal cysts and stones were discovered. A year later, more spinal hemangioblastomas and renal stones were found. A year later, cerebellar lesions, as well as renal and pancreatic cysts were reported (see table 1).

CaseNotHPOs: HP:0002088; HP:0001392; HP:0005264; HP:0001743 (abnormal lung morphology; abnormality of the liver; abnormality of the gallbladder; abnormality of the spleen)

CaseNotHPOFreeText: No lesions were observed in the lungs, liver, gallbladder, and spleen.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData:  N/A

Variant: p.N90del (c.268_270del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA645524783, https://reg.genome.network/redmine/projects/registry/genboree_registry/by_caid?caid=CA645524783

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: N90del (c.268_270del)

MultipleGeneVariants: N/A

GroupID: 13

Case: Sex unknown, Age unknown, German

DiseaseAssertion: VHL

FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114Vfs*45 (c.339delA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA645509026 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.339delA

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: G114Vfs*45 (c.339delA)

MultipleGeneVariants: N/A

That Pigeon Looks Just Like Michael Keaton<br /> The Late Show with Stephen Colbert

Definitely a late model Olivetti. Either a Studio 45, which was more common in the United States, or a Studio 46, both of which came in that color.

I'm leaning toward 46 because of some of the shape of the hood as well as the white variable button on the platen which I've only ever seen on the 46 while the 45s were typically black or had the button colored to match the body color.

https://mrmrsvintagetypewriters.com/collections/typewriter-accessories-parts/products/one-spool-nut-olivetti-typewriter-lettera-22-32-44-studio-45-dora-dl-underwood-315-screw-holder

Who were/are the Volga Russians? How many immigrated to the US in this decade?

Cite your source(s).

Massebah for pagan worship: - Exodus 23:24 (https://hypothes.is/a/r3m5QmyDEe6SC8eLYcJE1Q) - Hosea 10:1 (https://hypothes.is/a/4PK2GGyDEe6wZg_r2YpVCA ) - 2 Kings 18:4 - 2 Kings 23:14

Massebah for worship of Yahweh: - Genesis 28:18 Jacob's pillow (https://hypothes.is/a/NF5p8Gx6Ee65Rg_J4tfaMQ)<br /> - Genesis 31:44-45 Jacob and Laban's covenant - Exodus 24:4 - Joshua 24:25-27

Catherine Finnecy. (2022, February 11). SPI-M-O currently estimates that a combination of behavioural change...and mitigations (e.g. Testing, self-isolation) are currently reducing transmission by 20–45% [Tweet]. @cfinnecy. https://twitter.com/cfinnecy/status/1492213392681181184

This link to learning is a NYT article behind a paywall, we should look for a replacement that is truly free

AssayResult: 4.6

AssayResultAssertion: Normal

StandardErrorMean: 0.57

HGVS: NM_024675.3:c.2852C>T p.(Ser951Phe)

AssayResult: 83

AssayResultAssertion: Not reported

PValue: Not reported

Approximation: Exact assay result value not reported; value estimated from Figure 6C.

AssayResult: -21

AssayResultAssertion: Indeterminate

PValue: < 0.01

AssayResult: 109.7

AssayResultAssertion: Not reported

PValue: > 0.9999

Comment: Exact values reported in Table S3.

HGVS: NM_024675.3:c.956C>A p.(Ser319Tyr)

AssayResult: 99.69

AssayResultAssertion: Not reported

ReplicateCount: 2

StandardErrorMean: 3.09

Comment: Exact values reported in “Source Data” file.

AssayResult: 76.97

AssayResultAssertion: Not reported

ReplicateCount: 2

StandardDeviation: 3.1

StandardErrorMean: 2.19

Comment: Exact values reported in “Source Data” file.

HGVS: NM_024675.3:c.3119T>C p.(L1040S)

AssayResult: 12

AssayResultAssertion: Abnormal

ReplicateCount: 10

StandardErrorMean: 2.2

Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)

HGVS: NM_198056.2:c.4035G>T p.(Trp1345Cys)

AssayResult: 78

AssayResultAssertion: Normal

Comment: See Table S3 for details

AssayResult: 5.1

AssayResultAssertion: Abnormal

Comment: See Table S3 for details

HGVS: NM_000546.5:c.833C>G p.(Pro278Arg)