Case#: Male, Family #2, patient #4, onset at 48y.o

DiseaseAssertion: STGD

FamilyInfo: proband sister(#3) identical ABCA4 allele to proband, developed central vision issues. Proband son has complex allele w/ early onset cone-rod dystrophy. Proband daughter(#6) has complex allele mutation, central vision issues developed at 17. retinal exam showed atrophic macular lesions. Proband second daughter(patient #5, asymptomatic)

CasePresentingHPOs: HP:0012508, HP:0030500

CaseHPOFreeText:Proband presented with bull's eye macular lesions with no fundus flecks. Normal rod-mediated amplitudes, normal single-flash response, reduces 32-Hz flicker amplitude.

CaseNotHPOs: n/a

CaseNotHPOFreeText: maintained foveal sparing in both eyes 20/25+2 R.E, 20/25+1 L.E.

Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.

PreviouslyPublished: n/a

Variant: c.4139C>T (p.P1380L), BoldM1: c.5603A>T(p.N18681)[NM_000350.3(ABCA4):c.5603A>T (p.Asn1868Ile) - Variation ID 99390], M2: c.[1622T>C; 3113C>T] (p.[L541P; A1308V])

ClinVar: M1) 99390 M2) 99067

CAID: n/a

SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom

Case#: Female, Family #4, patient #8

DiseaseAssertion: STGD

FamilyInfo: Proband's daughter shares ABCA4 variant and struggled with difficulty focusing at age 19. BVCA 20/200 R.E and 20/80 in L.E.

CasePresentingHPOs: HP:0030500, HP:0007663, HP:0000608

CaseHPOFreeText: Proband's first symptom was difficulty with night vision occurring at 45 y.o, BVCA at 50 y.o in both eyes was 20/20. atrophy in macula and Stage 2 fundus flecks identified.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.1622T>C (p.Leu541Pro), NM_000350.3(ABCA4):c.1957C>T (p.Arg653Cys)

ClinVar: M2) 99067, M5) 99108

CAID: n/a

SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom

Case#: Male, Family#3, Proband M1, M2: II,1 on pedigree

DiseaseAssertion: STGD

FamilyInfo: mother of proband has p.N18681 and p.P1380L mutations and is asymptomatic with no changes to NIR-AF and SD-OCT. Treated with 400mg of hydroxychloroquine for lupus prior to imaging. Non-affected father.

CasePresentingHPOs:HP:0007663, HP:0000493

CaseHPOFreeText: Proband has reduced visual acuity and issues reading with BCVA 20/200 in R.E and 20/50-2 in L.E. Oval foveal lesions with stage 2 flecks. Visual acuity reducing starting at age 10.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.

PreviouslyPublished: n/a

Variant: M1:p.P1380L, complex allele: M2: p.N18681 and IVS38:c.5461-10T>C. M3: c.4139C>T(p.P1380L)

ClinVar: M1) 99390 M2) 99067 M3) Variation ID: 7904

CAID: n/a

SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom

Case#: Patient 1, Female, age 40

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0000007

CaseHPOFreeText: Patient diagnosed with STGD type 1, presenting with retinal pigment atrophy as well as other symptoms typical of STGD1 with reduced visual acuity. Patient daignosed at age 16.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Patient ABCA-4 gene sequenced via Sanger sequencing of all 50 exons, Splice variants were identified by synthesized cDNA from RNA isolation with RT-PCR analysis with exonic primers.

PreviouslyPublished: Variant 1 identified in association with retinal dystrophy in these PMC articles: 23982839, 25082829, 25082885, 28327576

Variant: NM_000350.3(ABCA4):c.859-9T>C, NM_000350.3(ABCA4):c.303-3C>G

ClinVar: 3249248, 859348

gnomAD total allele frequency: 0.005% of var . 1

CAID: n/a

SupplementalData: Fig 1: Minigene RNA analysis of splice variants. A: genomic region of exon 40 on ABCA-4. B: genomic regions of exons 39-41 to investigate specific variant:oncanonical splice site variant c.5714+5G>A Fig 2: overview of wild-type midigene splice constructs of ABCA-4 and locations of 47 different non canonical splice site variants Fig 3: Overview of splice defects from nine different non canonnical splice variants in ABCA-4 gene. Fig 4: percentages of normal ABCA-4 transcripts as a result of noncanonical splice variants using electrophoresis system analysis. Table 1: Non canonical splice variants and observed protein affects.

Case#: Female, family #5, Patient #20

DiseaseAssertion: STGD

FamilyInfo: Proband's sister presented with same clinical prognosis. Sister diagnosed with pattern dystrophy and photoaversion at age 57, with difficulty seeing at night. Sister has nuclear sclerotic and cortical cataracts in both eyes.

CasePresentingHPOs: HP:0000662, HP:0000603, HP:0000603, HP:0000493

CaseHPOFreeText: Proband presented with localized blur at age 62, (late onset) in her left eye. BVCA 20/20-3 and 20/20-2 at age 70. Also has macular lesions with stage 2 fundus flecks.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.

PreviouslyPublished: n/a

Variant: p.N18681, IVS36:c.5196+1G>A

ClinVar: M2) 99067, M6) 99351

CAID: N/A

SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom

Case#: Female, family #5, Patient #20

DiseaseAssertion: STGD

FamilyInfo: Proband's sister presented with same clinical prognosis. Sister diagnosed with pattern dystrophy and photoaversion at age 57, with difficulty seeing at night. Sister has nuclear sclerotic and cortical cataracts in both eyes.

CasePresentingHPOs: HP:0000662, HP:0000603, HP:0000603, HP:0000493

CaseHPOFreeText: Proband presented with localized blur at age 62, (late onset) in her left eye. BVCA 20/20-3 and 20/20-2 at age 70. Also has macular lesions with stage 2 fundus flecks.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.

PreviouslyPublished: n/a

Variant: p.N18681, IVS36:c.5196+1G>A

ClinVar: M2) 99067, M6) 99351

CAID: N/A

SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom

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gene name: DICER 1 PMID (PubMed ID): 33570641 HGNCID: n/a Inheritance Pattern: autosomal dominant Disease Entity: benign and malignant tumor mutation Mutation: somatic Zygosity: heterozygous Variant: n/a Family Information: n/a Case: people of all sexes, ages, ethnicities and races participated CasePresentingHPOs: individuals with DICER1-associated tumors or pathogenic germline DICER1 variants were recruited to participate CasePreviousTesting: n/a gnomAD: n/a

GeneName: DICER1 PMID: 29762508 HGNCID: Can't find Inheritance: Autosomal Dominant Disease Entities: Endocrine and Reproductive Tumors Mutation: Somatic and germline Zygosity: Heterozygous Mutant: Can't find Family: Can't find

GeneName:DICER1 PMID (PubMed ID): PMCID: PMC6418698 PMID: 30672147 HGNCID: NOT LISTED<br /> Inheritance Pattern: Autosomal Dominant Disease Entity: Cancer; benign and malignant tumors including pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig cell tumors, multinodular goiter, Thryoid cancer, rhabdomyosarcoma, and pineoblastoma. Mutation: Somatic missense variation Mutation type: missense Zygosity: None stated Variant: unregistered…. Family Information: Characterize germline variants in familial early-onset clorectal cancer patients; The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation. CasePresentingHPOs: uterine and rectal cancers in germline mutation