Case#: MD-0170 Proband, 14yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family MD-0170

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCR400

PreviouslyPublished: unclear

Variant: c.4457C>T (p.Pro1486Leu); c.1222C>T (p.Arg408*)

ClinVar: 99283

CAID: CA227192

SupplementalData: n/a

Case#: Family MD-0084 Proband, 7yo at onset

DiseaseAssertion: AR Stargardt

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)." VA loss, VF loss, BCVA=<0.05/<0.05

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: PMID: 16917483 (variant not found in this paper); PMID: 19959634

Variant: c.6410G>A (p.Cys2137Tyr) homozygous, found by ABCR400 + dHPLC + HRM + MLPA

ClinVar: 2202779

CAID: CA341277358

SupplementalData:

Case#: Family MD-0242 Proband, 18yo at onset, Spanish

DiseaseAssertion: AR Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCR400 microarray, direct sequencing for confirmation

PreviouslyPublished: n/a

Variant: c.1715G>C p.Arg572Pro

ClinVar: 99073

CAID: CA226919

SupplementalData:

Case#: Fishman Patient #22, male, 28yo

DiseaseAssertion: Stargardt dystrophy or fundus flavimaculatus

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: dark choroid, diffuse yellowish white flecks in the fundus, 20/400 OU, central scotoma

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: only one variant found: c.6383A>G (p.His2128Arg) Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCRgene.

ClinVar: 99455

CAID: CA227399

SupplementalData:

Case#: Patient#010046, Chinese, 28yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." stage 2( numerous yellow-whitish flecks throughout the posterior pole) BCVA=0.05/ 0.05

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; p.A1773V phase unknown

ClinVar: 2202780

CAID: CA341277622

SupplementalData: supplementary table S3 has phenotype information

Case#: STGD138, 15-19yo at onset, German

DiseaseAssertion: STGD

FamilyInfo: segregation in family

CasePresentingHPOs:

CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

PreviouslyPublished: n/a

Variant: IVS13+1G→A; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

ClinVar: 7879

CAID: CA119128

SupplementalData: n/a

Case#: STGD87, 10-14yo at onset, German

DiseaseAssertion: STGD

FamilyInfo: segregation in family

CasePresentingHPOs:

CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

PreviouslyPublished: n/a

Variant: Q1750X; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

ClinVar: 7879

CAID: CA119128

SupplementalData: n/a

Case#: Maia-Lopes Family 11 Proband 4613, Portuguese, 9yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family 11

CasePresentingHPOs:

CaseHPOFreeText: severe central fundus changes, vision: FC/FC

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, dHPLC

PreviouslyPublished: n/a

Variant: c.[4926C>G(35)]+[5041_5055del(36)] / c.32T>C(1); p.(Ser1642Arg [10])+(Val1681_Cys1685del [10])/p.Leu11Pro

ClinVar: 99217

CAID: CA227106

SupplementalData: n/a

Case#: 93RE proband, Spanish

DiseaseAssertion: cone rod dystrophy

FamilyInfo: 1 affected sibling with the same genotype. het, carrier parents

CasePresentingHPOs: n/a

CaseHPOFreeText:

CaseNotHPOs: n/a

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6410G>A (p.C2137Y); c.3988G>T (p.E1330X) found on WES. Cosegregation with GNAT2, ZNF513, OPA1, RP1L1

ClinVar: 2202779

CAID: CA341277358

SupplementalData: pedigree with genotype in supplemental file

Case#: Hwang Case 3, female, 15yo at report, 7yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: Family history was not significant for ocular disease.

CasePresentingHPOs: HP:0500087, HP:0011507

CaseHPOFreeText: difficulty reading materials held greater than 6 inches from her eyes, decreased visual acuity since age seven. BCVA was 20/150 OU. Posterior segment exam and autofluorescence was significant for bilateral central atrophy and pisciform fleck atrophy involving the peripapillary, macular, and peripheral regions OU (Figure 3, A and B).

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

PreviouslyPublished: n/a

Variant: P1380L and R2030Q

ClinVar: 7904

CAID: CA129033

SupplementalData: n/a

Case#: Hwang Case 2, female, 19yo at report, 18yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: Family history was not significant for ocular disease

CasePresentingHPOs: HP:0007663, HP:0500087, HP:0011507

CaseHPOFreeText: difficulty reading, particularly in dim light; gradual difficulty in focusing. Visual acuity measured 20/40 OD and 20/150 OS. bilateral central atrophy, multiple fleck lesions, multiple clumps of yellowish deposits at the level of the retinal pigment epithelium in the posterior pole surrounded with some pigment clumping, and no evidence of atrophy of the retinal pigment epithelium. Autofluorescence imaging revealed multifocal atrophic lesions involving the central macula and peripheral hyperautofluorescent flecks OU. The peripapillary regions demonstrated atrophic flecks OU without confluent atrophy (Figure 2, A and B).

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

PreviouslyPublished: n/a

Variant: P1380L homozygous

ClinVar: 7904

CAID: CA129033

SupplementalData: n/a

previously reported in PMID: 26377081

Case#: Patient 8, 13yo at report, British Columbia, Canada

DiseaseAssertion: Stargardt disease

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: stage 4 Fishman classification (extensive choroid and RPE atrophy throughout the fundus, decreased ERG cone and rod amplitudes, and moderate to severe peripheral field restriction). Visual acuity= 20/200

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: exons and exon-intron boundaries of ABCA4, CNGB3, and ELOVL4 were sequenced

PreviouslyPublished: n/a

Variant: L541P; A1038V phase unknown, but likely a complex allele

ClinVar:

CAID: CA226911

SupplementalData: n/a

Case#: Patient #16, male, 6yo at onset, Brazilian

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: type II (an area of foveal hypofluorescence surrounded by an area with a heterogeneous appearance and hyperautofluorescent and hypoautofluorescent points that extend to the temporal arcades, giving the retina a reticulate appearance). visual acuity: OD=20/150, OS=20/200

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.4720G>T p.(Glu1574*), no second variant. NGS and conclusive molecular testing regarding other Stargardt genes were excluded

ClinVar: 1460063

CAID: CA341283936

SupplementalData: n/a

Case#: Patient#010477, Chinese, male, 18yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." BCVA=0.4/ 0.5

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; c.2255G>T p.(Ser752Ile) phase unknown

ClinVar: 2202780;

CAID: CA341277622;

SupplementalData: supplementary table S4 has phenotype information

Case#: Patient#010382, Chinese, male, 29yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." BCVA=0.4/ 0.6

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; c.6050G>A p.(Cys2017Tyr) phase unknown

ClinVar: 2202780;

CAID: CA341277622;

SupplementalData: supplementary table S4 has phenotype information

This variant is found without ala1038val in patient 5. Patient 5 is a 36yo white female. Visual acuity= OD:10/120, OS:10/60-1. Central scotome. Type 1 fundus=diffuse pigmentary degenerative changes. Cone responses more reduced than rod amplitudes on ERG. Second variant: Asp600Tyr. Phase not confirmed

Case#: Patient 721, male, 41yo at entry

DiseaseAssertion: Stargardt disease

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: category IIA (autosomal recessive stargardt disease)

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one or more of the following approaches: automated Sanger sequencing with an ABI 3730xl sequencer, allele-specific genotyping with a Fluidigm EP1, amplification refractory mutation system (ARMS 17), chromosomal microarray analysis, and/or plasmid cloning of PCR products followed by Sanger sequencing. WES, WGS

PreviouslyPublished: n/a

Variant: c.6416G>C p.Arg2139Pro; c.2588G>C p.Gly863Ala. confirmed in trans

CAID: CA10611614

SupplementalData: supplemental table 1

Case#: 43-year old man, German descent, onset within first decade of life

DiseaseAssertion: STGD1

FamilyInfo: Family pedigree shown in Figure 1.

CasePresentingHPOs: HP:0011463, HP:0000533, HP:0000580, HP:0030500, HP:0011507, HP:0000548, HP:0000510, HP:0007703, HP:0007663, HP:0000512, HP:0000610

CaseHPOFreeText: Retinal vessels were visibly attenuated.

CaseNotHPOs: n/a

CaseNotHPOFreeText: Peripapillary region around the optic nerve had no disease related changes.

Genotyping Method: Illumina MiSeq platform, Array-CGH analysis

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr), NM_000350.3(ABCA4):c.4539+2028C>T

ClinVar: 99065, 236116

SupplementalData: n/a

This variant was found on one allele of a Stargardt patient, but no additional details are provided about the patient or the other allele. A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to evaluate the entire exonic and flanking intron sequence of the ABCA4 gene

Case#: Eisenberger Patient 92, female, 31yo, German

DiseaseAssertion: Autosomal dominant RP

FamilyInfo: non-consanguineous

CasePresentingHPOs:

CaseHPOFreeText: "The diagnoses of all patients were established by medical history, family history and detailed clinical evaluation of vision. Ophthalmological examination included stereoscopic funduscopy, standard ERG, perimetry, measurement of dark adaptation, and determination of best-corrected visual acuity in most patients."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS for the exons of 55 RP and LCA genes, Sanger for confirmation

PreviouslyPublished: n/a

Variant: Allele 1: RHO c.180C>A p.Tyr60; Allele 2*: ROM1: c.178C>A p.Pro60Thr; c.323C>T p.Thr108Met;

ABCA4: c.1654G>A p.Val552Ile; c.5714+5G>A; <br /> RP2: c.844C>T p.Arg282Trp; <br /> RPGRIP1: c.2510C>G p.Ala837Gly

ClinVar:

CAID: CA239745

SupplementalData: n/a

Annotating here since unable on the PDF.

Case 3 is a 6yo male. VA: OD: 20/150, OS: 20/200. Proband had macular atrophy and flecks at the posterior pole. In the autofluorescence exam, there was peripapillary sparing of the hyper-autofluorescent flecks. On OCT images the atrophic areas at the macula correlated to disruption of the elipsoid layer and decrease in the foveal thickness. OCT showed loss of the photoreceptor layer and EPR layer. Proband has only 1 ABCA4 variant, so not eligible for PP4. Also has a variant in PROM1 (p.Ala643Gly). ABCA4, PROM1, and ELOVL4 genes sequenced by next-generation sequencing (NGS) test.

PMID: 39421326 (PMCID: PMC11675205)

Gene: ABCA4

HGNC ID: 34

Case#: Patient 24 (male)

DiseaseAssertion: STGD (Stargardt disease)

FamilyInfo: Caucasian family from Germany. Patient has two siblings carrying the variant but they are not clinically affected according to pedigree information.

CasePresentingHPOs: Decreased central visual acuity (HP:0000545) Macular atrophy (HP:0007754) Retinal flecks (HP:0030638) Abnormal fundus autofluorescence (HP:0030647) Macular degeneration (HP:0007754) Abnormal electroretinogram (HP:0000763)

CaseHPOFreeText: Male patient diagnosed before age 50 with Stargardt disease. Best corrected visual acuity (BCVA) approximately 0.05–0.2. Fundus imaging shows paracentral scotoma, macular atrophy, and hyperfluorescent flecks with sparing of the fovea. Autofluorescence demonstrates hyperreflective spots and patchy lesions with parafoveal involvement.

CaseNotHPOs: None explicitly reported.

CaseNotHPOFreeText: Pattern-like distribution of lesions noted on clinical examination.

Genotyping Method: Whole-exome sequencing (WES) with an in-house RD-associated gene panel including 619 candidate and disease-associated genes.

PreviouslyPublished: No (novel complex deep-intronic allele described in this study).

Variant: c.[1555-5882C>A;1555-5784C>G]

ClinVar: Not reported in ClinVar in the provided information.

CAID: CA272741; CA227172

SupplementalData: Segregation data and functional splicing analysis available in the supplemental data (Table S1, Figure S1) of the article.

Case#: Bertelsen Patient D023, female, 9yo at onset

DiseaseAssertion: generalized choriocapillaris dystrophy

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: end-stage generalized choriocapillaris dystrophy characterized by semiconfluent multifocal areolar outer retinal atrophy, the severity of which decreases with increasing eccentricity. Central patches of visible sclera are surrounded by coarse confluent hyperpigmentation. The periphery shows isolated or clustered hyperpigmentation. In and around the fovea there is pronounced atrophy of the retinal pigment epithelium, the photoreceptor layer, and the outer nuclear layer and intraretinal hyperreflective material corresponding to the hyperpigmentation

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: microarray

PreviouslyPublished: n/a

Variant: c.203C>T p.P68L; c.3329-2A>G

ClinVar: 99113

CAID: CA226972

SupplementalData: n/a

Case#: Patient #43, male, 9yo at onset, 16yo at report, German

DiseaseAssertion: macular dystrophy or cone-rod dystrophy

FamilyInfo: inheritance= sporadic. phase not confirmed, but no other affected family members and no parental consanguinity

CasePresentingHPOs:

CaseHPOFreeText: reduced visual acuity, erg scotopic= reduced, erg-photopic=reduced

CaseNotHPOs:

CaseNotHPOFreeText: syndromic retinal disease, age-related macular degeneration, central serous retinopathy, autoimmune retinopathy, retinal vascular disease, achromatopsia, X-linked retinoschisis, North Carolina macular dystrophy

CasePreviousTesting: n/a

GenotypingMethod: Sanger sequencing of ABCA4

PreviouslyPublished: n/a

Variant: c.3098del (p.Lys1033Serfs*51); c.3243G>T (p.Lys1081Asn)

ClinVar: 236516

CAID: CA10581650

SupplementalData: Supplementary table 1

This variant is found in Table S5. "Five probands with one ABCA4 disease-associated allele" Proband #89. Since this proband has only one variant they are not eligible for PP4

Case#: Patient STG-16, 13yo at onset, Argentina

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: BCVA=0.7/0.7, FA=3B, AF pattern=2, OCT showed decreased retinal thickness with disruption of external layers

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS of ABCA4 (NM_000350.2), ELOVL4 (NM_022726.3), PROM1 (NM_006017.2), and CNGB3 (NM_019098.4)

PreviouslyPublished: n/a

Variant: c.4457C>T (p.Pro1486Leu); c.1804C>T (p.Arg602Trp)

ClinVar: 99283

CAID: CA227192

SupplementalData: supplementary table 2 has genotype/phenotype info

Case#: Proband 95-0103, Spanish, onset at 8yo

DiseaseAssertion: cone-rod dystrophy

FamilyInfo: Family RP-0298. Affected sister, 95-0101, with same genotype

CasePresentingHPOs: HP:0001133, HP:0000529, HP:0000662, HP:0000512, HP:0000543, HP:0007737, HP:0007641, HP:0007787

CaseHPOFreeText: BCVA=0.1/0.1; ERG: scotopic-Low amplitude, normal latency, photopic-abolished, mixed-diminished a and b waves; dense pigment accumulation at macular region;, bilateral posterior subcapsular cataract.

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: 19365591

Variant: c.4720G>T p.E1574; c.950delG p.G317Afs57. WES, All patients were previously tested and all resulted to be negative for known autosomal recessive retinitis pigmentosa (ARRP) or Leber Congenital Amaurosis (LCA) mutations by microarray screening

ClinVar: 1460063

CAID: 341283936

SupplementalData: Table S2 has phenotype details

Case#: Family AR534 Proband 05

DiseaseAssertion: Stargardt

FamilyInfo: Three paternal cousins are affected with STGD, with onset between the ages of 8 and 10 (unaffected het parents). The proband’s parents reported no visual impairment (father has P1380L/wt, mother has W821R/wt), but the paternal grandmother had been diagnosed previously with age-related macular degeneration at age 68 (het for P1380L). Subsequently, she developed hemorrhagic detachment of the macula, and a diagnosis of exudative AMD was made at age 74

CasePresentingHPOs:

CaseHPOFreeText: central visual impairment at age 11, retinal atrophy of the macula and a few peripheral flecks, A dark choroid was observed on fluorescein angiography,

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Direct DNA sequencing of the 50 exons and flanking intronic regions of ABCR. Heteroduplex analysis

PreviouslyPublished: n/a

Variant: c.2461T>A (p.W821R); c.4139C>T (p.P1380L). Phase confirmed. Also has 2 synonymous variants (c.5682G>C and c.5814A>G)

ClinVar: 7904

CAID: CA129033

SupplementalData: n//a

Case#: Patient #P023, Korean

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: no individual phenotype information, group only

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: exome sequencing: c.6289C>T p.Pro2097Ser; c.3547G>T p.Gly1183Cys; c.3035_3037delACA p.Asn1012Ile

ClinVar: CA341277622

CAID: 2202780

SupplementalData: n/a

paper not publicly available, but is said to contain this variant based on LOVD entry. requested from library.

Update: Received paper from library. 1 proband in Figure 1 has this variant, but cannot access the supplementary info to see the individual phenotype information. Affected maternal aunt with homozygous c.4605_4606ins-non-segregation.

Case#: Aguirre-Lamban Unlabeled Proband, Spanish

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "Diagnosis of STGD was determined according to a bilateral central vision loss with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; typical dark choroid observed by fluorescein angiography; and normal to subnormal electroretinograms (ERGs)."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, direct sequencing, dHPLC, haplotype analysis

PreviouslyPublished: n/a

Variant: c.1654G>A p.Val552Ile, interpreted as non-pathogenic, suggested to be a polymorphism

CAID: CA239745

SupplementalData: n/a

Case#: Family 16, P37, female, Netherlands 13yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: 1 affected sibling with same genotype

CasePresentingHPOs:

CaseHPOFreeText: visual acuity: OD=0.22, FAF images consistent with STGD1

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Sanger

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.859-506G>C

ClinVar: 438100

CAID: CA26843511

SupplementalData:

In supplemental table S2, Case LL345 is listed as "likely solved" with a clnical diagnosis of Stargardt disease. Proband is compound heterozygous for c.4139C>T p.(Pro1380Leu) and c.4918C>T p.(Arg1640Trp).

In Supplemental table S1, this proband is a female, 25yo at report, 11yo at onset. Decreased VA: 0.08/0.05, emmetropia OU

Case#: Patient 1, male, Caucasian, onset at 20yo, USA

DiseaseAssertion: ABCA4

FamilyInfo: No family history of retinal disease.

CasePresentingHPOs: HP:0007677, HP:0030603, HP:0030500, HP:0030636, HP:0004328, HP:0012372

CaseHPOFreeText: Bilateral central vision loss, progressive decline in visual acuity (20/60 both eyes), foveomacular vitelliform lesions with fluid accumulation, optical gap lesions progressing to cavitated appearance after fluid resorption, thinning and abnormal reflectivity of photoreceptor layers, near-infrared autofluorescence abnormalities in lesion-adjacent regions

CaseNotHPOs: HP:0000510, HP:0000511

CaseNotHPOFreeText: No generalized rod or cone dysfunction on full-field electroretinogram, EOG findings not consistent with bestrophinopathy (Arden ratio 1.62)

Genotyping Method: Exome sequencing

PreviouslyPublished: None

Variant: NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu), NM_000350.3(ABCA4):c.4139C>T (p.Pro1380Leu)

ClinVar: ClinVarID:7888, ClinVarID:7904

CAID: N/A

SupplementalData: N/A

Case#: Sporadic RP Patient 087, male, Chinese, 30yo at report

DiseaseAssertion: RP

FamilyInfo: n/a, sporadic case

CasePresentingHPOs:

CaseHPOFreeText: "The sporadic RP patients generally showed pubertal night blindness, restricted peripheral vision, progressive vision loss, overall bone-spicule pigmentation of the retina, attenuation of retinal vessels, and the flattening of the rod and cone ERG responses."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: WES with Sanger sequencing confirmation

PreviouslyPublished: no

Variant: c.6397T>C p.(C2133R)

ClinVar: 2021273

CAID: CA341277387

SupplementalData:

Case#: Patient #133, Chinese

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs: n/a "Diagnosis of STGD was based on the clinical manifestations" is all that is stated

CaseHPOFreeText: n/a

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

PreviouslyPublished: n/a

Variant: c.6289 C>T p.(P2097S); c.4605_4606insT p.(V1535fs)

ClinVar: 2202780

CAID: CA341277622

SupplementalData: info found in table S2

Case#: Braun Family 8 Proband (from left to right, top to bottom of available pedigrees), female

DiseaseAssertion: Stargardt

FamilyInfo: Unaffected carrier parents. c.5196+1137G>A maternally inherited; c.4577C>T (p.T1526M) paternally inherited

CasePresentingHPOs:

CaseHPOFreeText: "five or more of the following features of ABCA4-associated retinal disease: decreased visual acuity before age 20, decreased visual acuity as the first visual symptom, symmetrical fundus findings, pisciform flecks, beaten metal macular atrophy, bulls-eye maculopathy, peripapillary sparing, vermillion fundus, masked choroid on fluorescein angiography, nummular pigment overlying extensive macular atrophy, central outer retinal atrophy on optical coherence tomography and central scotomas on Goldmann perimetry."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one plausible disease-causing mutation detected in ABCA4 after assessing the entire coding sequence and canonical retinal splice junctions with automated bidirectional Sanger sequencing using an ABI 3730 sequencer

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.4577C>T (p.T1526M)

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

PMID: 29706639

Gene: ABCA4

HGNCID: HGNC:34

MonDO: MONDO:0019353

Bioinformatic analyses of an SQL-based database containing 12272 variants that appear in 178 IRD genes in 5706 individuals of Ashkenazi Jewish origin based on the gnomAD database (version 2) and variants that were published in the scientific literature that was extracted from HGMD. Authors extracted information regarding IRD variants from various sources (including data of 5706 Ashkenazi Jewish (AJ) samples and a large cohort of Israeli patients with IRDs) to estimate carrier frequency of IRD mutations in different subpopulations in Israel. Two major databases aiming to estimate carrier frequency of IRD mutations in the Israeli population (Fig. 1): “gnomAD-AJ-IRD DB” containing data of 5706 AJ controls extracted from gnomAD and “HW-IRD DB” containing data extracted from our cohort of Israeli patients with IRDs.

See Fig 2 for breakdown of variants analyzed.

The final DB (IRDB) (Fig. 1 and Table S7) includes all 399 variants from “gnomAD-AJ-IRD DB” and “HW-IRD DB” that were considered here as pathogenic mutations in 111 known IRD genes.

To establish the “HW-IRD DB” (Fig. 1), we collected data on Israeli IRD patients with a known cause of disease (a cohort of >2000 IRD families). The HW-IRD DB includes 289 pathogenic mutations (Fig. 1) that were identified in IRD patients who have biallelic variants.

SupplementalData: S7, carrier frequency data for each mutation in all nine studied subpopulations. Carrier frequency was calculated as 2pq where p = 1 − q and q was calculated as the root square of the number of homozygous patients plus half the number of compound heterozygous patients divided by the population size

Variant: NM_000350.2:c.4895dup,p.Asn1632fs

CAID: CA915941330

Case: Ashkenazi Jewish patient with inherited retinal disease, STGD, CRD

CasePresentingHPOs: HP:0000548 (Cone/cone-rod dystrophy, CRD)

CaseHPOFreeText: Stargardt disease (STGD)

Case#: Patient #15, Moorfields Eye Hospital, London, UK, female, 39yo at onset, 51yo at report,

DiseaseAssertion: ABCA4-Associated Retinopathy, clinical diagnosis of STG

FamilyInfo: no additional family-member WGS data available

CasePresentingHPOs:

CaseHPOFreeText: BCVA= OD: 6/9, OS: 6/9, Fishmann Classification=2 (fleck-like lesions anterior to the vascular arcades and/or nasal to the optic disc), early changes to foveal photoreceptors, Extent of FAF abnormalities with Regard to Vascular Arcades: beyond. ffERG Group: 1(normal). PERG: Abnormal. FAF in Fig. 1B. characteristic yellow-white pisciform flecks in the RPE of the posterior pole that were hyperautofluorescent on FAF imaging or progressive atrophy of the macular RPE

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCA4 mutation screening was performed by next-generation sequencing, sequenced as part of the retinal panel at the Molecular Vision Lab

PreviouslyPublished:

Variant: c.5196+1137G>A p.[=,M1733Efs∗78] c.[1715G>A;2588G>C] p.[(R572Q;G863A,G863del]

ClinVar: 7900

CAID: CA226918

SupplementalData:

Case#: Case 3, male, onset at 24yo, Italy

DiseaseAssertion: STGD1

FamilyInfo: third-degree consanguineous parents; both parents healthy heterozygous carriers of the ABCA4 variant

CasePresentingHPOs: HP:0000529, HP:0007754, HP:0000518

CaseHPOFreeText: progressive deterioration of vision at age 24. Bilateral macular dystrophy and diffuse lens opacities on ophthalmologic examination. OCT, ERG, and VEP consistent with Stargardt maculopathy.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: NGS (custom enrichment panel), Illumina NextSeq550; variant confirmed by Sanger sequencing.

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.2828G>A (p.Arg943Gln), homozygous; rs1801581

ClinVar: Variation ID: 7913

CAID: n/a

SupplementalData: n/a

Case#: DNAID 072884/Pat255, female

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "In classic STGD1, loss of central vision starts around the second decade of life, but both early- and late-onset subtypes have been extensively described." No patient-specific details provided

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: smMIPs sequencing of the complete ABCA4 locus

PreviouslyPublished: n/a

Variant: c.1519G>T (p.Asp507Tyr); c.5312+3A>T (p.Asn1734Glyfs*14) phase not confirmed

CAID: CA958508

SupplementalData: tables s9 and s11

Case#: DNAID 072888/Pat258, female

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "In classic STGD1, loss of central vision starts around the second decade of life, but both early- and late-onset subtypes have been extensively described." No patient-specific details provided

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: smMIPs sequencing of the complete ABCA4 locus

PreviouslyPublished: n/a

Variant: c.6416G>C (p.Arg2139Pro); c.3323G>A (p.Arg1108His)

CAID: CA10611614

SupplementalData: tables s9 and s11

This variant is listed in supplementary tables S2 and S3. Proband TI-50 is a "solved" patient, meaning the phenotype matches the genotype. Homozygous female with MD/CORD- all that is provided.

Case#: Patient #35, male, 35yo at report, 14yo at onset,

DiseaseAssertion: STGD

FamilyInfo: family 30, segregation was noted as "yes" but no other details provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod:

PreviouslyPublished: n/a

Variant: allele 1: A1038V;L541P allele 2: G818E

ClinVar: 99135

CAID: CA227000

SupplementalData: supplemental table 1

Case#: Patient 4, Female, Caucasian, 33yo

DiseaseAssertion: STGD1

FamilyInfo: One of eight siblings; four affected. Disease segregates with ABCA4 variants consistent with autosomal recessive inheritance. Parents are deceased and can't be tested.

CasePresentingHPOs: HP:0007663, HP:0007754, HP:0025147, HP:0007924, HP:0011507

CaseHPOFreeText: gradual decline in visual acuity over 9 years, BCVA 20/300 OU, bilateral beaten-bronze appearance of the macula, numerous perimacular yellow flecks, fluorescein angiography showing hyperfluorescence in the posterior pole and dark choroid in the periphery

CaseNotHPOs: N/A

CaseNotHPOFreeText: absence of central hypofluorescence on fluorescein angiography (present in affected siblings but not this patient)

Genotyping Method: SSCP analysis; Taq Dyedeoxy Terminator Cycle Sequencing kit

PreviouslyPublished: N/A

Variant: NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala), NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr)

ClinVar: ClinVarID:7879, ClinVarID:99065

CAID: N/A

SupplementalData: Segregation and sequencing data (Figures 1, 4)

Case#: Liu Proband A034, Chinese, female

DiseaseAssertion: Stargardt

FamilyInfo: Mother has the Pro68Leu variant, but the father was not genotyped to know the phase of the second variant. Proband's daughter also has the Pro68Leu variant, but is unaffected.

CasePresentingHPOs:

CaseHPOFreeText: no individual details provided

CaseNotHPOs:

CaseNotHPOFreeText: patients with other ocular diseases, such as choroidal neovascularization, glaucoma, and diabetic retinopathy, or were undergoing treatments/therapeutic trials were excluded.

GenotypingMethod: Either eye gene-enriched (from 36 to 450 target genes) panel-based next-generation sequencing (NGS). Sanger bi-directional sequencing was conducted to confirm the rare candidate variants (allele frequency: less than 1.0% of the general population) and to perform the co-segregation analysis

PreviouslyPublished: n/a

Variant: c.203C>T p.(Pro68Leu); c.3883_3884del p.(Glu1295Lysfs*126)

ClinVar: 99113

CAID: CA226972

SupplementalData: S1 only provides group demographics for the different clinical classifications (fundus grade, FAF type, etc)

Case#: Sporadic Case #16, Mexican

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosis based on: "onset of symptoms in childhood or early adulthood (before 20 years of age), bilateral central vision loss (central and peripheral visual field computerized testing), a retinal “beaten-bronze” foveal appearance and/or yellow-whitish flecks from the posterior pole to the mid periphery, normal caliber of the retinal vessels, no pigmented bone spicules in the retinal periphery, a normal to subnormal electroretinogram, and a typical dark choroid in fluorescein angiography."

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: allele 1: c.2453G>A (p. G818E); c.5824G>C (p. E1942Q) allele 2: c.6384A>G (p.H2128R) direct sequencing of exons of ABCA4

ClinVar: 867010

CAID: CA957117

SupplementalData: n/a

This variant is found in compound heterozygosity with c.6089G>A p.(Arg2030Gln) in family MD-1001 in this study. No phenotype information provided. Not eligible for PP4 due to age of onset not being provided.

This variant is found on pg 16 in proband 14075. Compound heterozygous for c.6817-2A>C. MEH institute (UK). Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

Case#: Pt 7, male, 60yo at report, onset between 6-49yo, Irish

DiseaseAssertion: Stargardt

FamilyInfo: family 5

CasePresentingHPOs:

CaseHPOFreeText: VA: OD=6/36 OS=6/120, FAF and OCT in figure 2, FAF WRT vascular arcades=beyond, beaten bronze appearance, yellow flecks centrally, peripapillary sparing, central retinal thickness: OD=100 microns OS=117 microns, optical coherence tomography (OCT) atrophy horizontal width: OD=6000 microns OS=5446 microns

CaseNotHPOs:

CaseNotHPOFreeText: bulls eye pattern, flecks peripherally

GenotypingMethod: Target capture NGS of the exons and known pathogenic intronic regions of ABCA4, whole-gene single molecule molecular inversion probe (smMIP) based sequencing of ABCA4 as well as 40 kb of flanking sequence, direct Sanger sequencing, or WGS

PreviouslyPublished: n/a

Variant: c.4539 + 2028C > T p.[= ,Arg1514Leufs*36]; c.2453G> A p.(Gly818Glu)

ClinVar: 99135; 236116

CAID: CA227000; CA10576057

SupplementalData: n/a

Case#: Klevering Patient 9369, female, Netherlands, 40yo at report, 8yo at onset

DiseaseAssertion: cone-rod degenerations/ ABCA4-associated retinal dystrophy resembling CRD

FamilyInfo: "In view of the reputedly normal visual acuity of the parents and the molecular defects, the inheritance pattern of the gene defects in these patients (individuals 9303, 9369, 9553, and 13163) was classified as autosomal recessive."

CasePresentingHPOs:

CaseHPOFreeText: Visual acuity: light perception OU. Fundoscopy: Irregular hypopigmentation, mainly in the posterior pole. In later stages: attenuated vessels and bone spicula temporal to the macula. Red-green defect of color vision. Perimetry: Central scotoma varying from 10–30°. ERG Cone (μV): OD-80 (80%), OS-140 (90%) from 12 yo (all ERG responses had been non-detectable since the age of 21). ERG Rod (μV): 160 (nl). Fundus photographs and fluorescein angiograms show CRD in the later stages with attenuation of the retinal arterioles and irregular pigmentation temporal to the macula. Narrowing of retinal vessels and bone spicula (Fig 1B). Fundus description (PMID: 10958761): atrophy of the RPE around the optic disk, bone spicules along arteries and venules in the mid-periphery, and attenuated arterioles (Fig 1D)

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: single-strand conformation polymorphism (SSCP) and direct-sequencing techniques to look for mutations in the 50 exons and flanking intron sequences of the ABCA4 gene

PreviouslyPublished: Maugeri et al (PMID: 10958761)

Variant: c.6601_6602delAG

CAID: CA227421

SupplementalData: n/a

Case#: Subject 20, 28yo, 18yo at first ffERG, Sweden, female

DiseaseAssertion: CRD, group 2

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: extensive atrophies in the posterior pole. peripheral pigmentations. few peripapillary changes. Normal thickness of the most central segment recorded on OCT. total absence of the PIL (photoreceptor integrity line) and RPE atrophy on the OCT B-scans. ETDRS VA score= 35, 35. Rod
ffERG= 38, 34 Ampl
(µV). Combined ffERG= 52, 57 Ampl
(µV). Cone
ffERG= 4, 5; 45.0, 42.5 Amp IT
(µV; ms). mERG sum= 1.0, 0.7 Ampl (µV). Group 2 with larger central scotomas from 10° to 35°

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Sequence analysis of the entire coding region of the ABCA4 gene was performed.

PreviouslyPublished: n/a

Variant: c.1654G>A; c.4363T>C

CAID: CA239745

SupplementalData: n/a

Case#: Hwang Case 4, male, 52yo at report, 45yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: Family history was not significant for ocular disease.

CasePresentingHPOs: HP:0000545

CaseHPOFreeText: declining vision OS, BCVA was 20/100 OD and 20/70 OS. Spherical refractive error measured −3.00 OD and −3.25 OS. Posterior segment examination was significant for central atrophy and classic peripheral pisciform flecks sparing the peripapillary regions OU (Figure 4, A and B). Autofluorescence imaging demonstrated inner atrophic flecks and outer hyperautofluorescent flecks. Moderate peripapillary hypoautofluorescence, but not atrophy, was present (Figure 4, C and D).

CaseNotHPOs: HP:0500087

CaseNotHPOFreeText:

GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

PreviouslyPublished: n/a

Variant: P1380L and S1696N

ClinVar: 7904

CAID: CA129033

SupplementalData: n/a

Case#: Hwang Case 1, US, male, 55yo at report, 18yo at onset

DiseaseAssertion: Stargardt disease

FamilyInfo: Family history was not significant for ocular disease

CasePresentingHPOs: HP:0007663, HP:0500087, HP:0000603, HP:0000512

CaseHPOFreeText: BCVA of 20/350 OD and 20/200 OS. Spherical refractive error measured −3.5 OD and −2.0 OS. Posterior segment examination and autofluorescence imaging were significant for sharply demarcated central and peripapillary zones of atrophy and the absence of fleck lesions (Figure 1, A–D). Humphrey visual fields demonstrated bilateral central scotomas with eccentric fixation at the inferior border.

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

PreviouslyPublished: n/a

Variant: P1380L and IVS40 + 5G>A

ClinVar: 7904

CAID: CA129033

SupplementalData: n/a

This variant is found on pg 11 in proband 18034. Compound heterozygous for c.2588G>C p.Gly863Ala. Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

This variant is found on pg 2 in proband 11019. Compound heterozygous for c.4532C>A, (p.Pro1511His). JHU institute (US). Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

This variant is found on pg 21 in proband 13047. Compound heterozygous for c.5882G>A p.Gly1961Glu. Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

Unable to annotate on PDF, so annotating here.

Case#: Proband #4, male, Chinese, onset at 12yo

DiseaseAssertion: stargardt

FamilyInfo: parents are deceased, so phase is unknown. daughter is an unaffected carrier of this variant

CasePresentingHPOs: HP:0025147, HP:0011507, HP:0000608

CaseHPOFreeText: BCVA=0.3/CF, mean retinal nerve fiber layer(µm)=167/154, Visual field(mean deviation)= 7.52/NA, fundus fluorescein angiography=type C (a pattern of speckled hypofluorescence and hyperfluorescence without central hypofluorescence)

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6289C > T p.(Pro2097Ser); c.4720G > T p.(Glu1574*) on targeted exome sequencing or WES

ClinVar: 2202780; 1460063

CAID: CA341277622; CA341283936

SupplementalData: n/a

Case#: Patient#010455, Chinese, male, 18yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." BCVA=0.01/ 0.01

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; c.4906_4908del p.(Asn1636del) phase unknown

ClinVar: 2202780;

CAID: CA341277622;

SupplementalData: supplementary table S4 has phenotype information

Case#: Patient#010046, Chinese, female, 28yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." stage 2( numerous yellow-whitish flecks throughout the posterior pole) BCVA=0.05/ 0.05

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: PMID: 26780318

Variant: p.P2097S; p.A1773V phase unknown

ClinVar: 2202780

CAID: CA341277622

SupplementalData: supplementary table S4 has phenotype information

Case#: Patient#010633, Chinese, female, 20yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." BCVA=0.05/ 0.05

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; c.3468C>G p.(Tyr1156*) phase unknown

ClinVar: 2202780;

CAID: CA341277622;

SupplementalData: supplementary table S4 has phenotype information

Case#: Cideciyan Case #86, male, 20.5yo at report

DiseaseAssertion: "clinical diagnosis within the spectrum of Stargardt disease or cone–rod dystrophy caused by ABCA4 mutations."

FamilyInfo: Parental segregation of the reported alleles confirmed. P87 is the proband's sibling, affected, same genotype

CasePresentingHPOs:

CaseHPOFreeText: LDF eccentricity along principal meridians [deg]: superior=16.9, inferior=11.7, temporal=18.9, inner nasal=9.6, outer nasal=18.9

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS

PreviouslyPublished: PMID: 24550365

Variant: c.203 C>T p.Pro68Leuc.5882 G>A p.(Gly1961Glu); c.5882 G>A p.(Gly1961Glu). Phase confirmed.

ClinVar: 99113

CAID: CA226972

SupplementalData: table s1

Case#: Family MD-0247/ARDM-247 Proband, 12yo at onset

DiseaseAssertion: AR cone rod dystrophy

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)." VA loss, VF loss, BCVA=0.05/0.1, cone-pattern on ERG

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6410G>A (p.Cys2137Tyr); c.3386G>T (p.Arg1129Leu) found by ABCR400 + dHPLC + HRM

ClinVar: 2202779

CAID: CA341277358

SupplementalData: n/a

Case#: Maia-Lopes Family 18 Proband 5709, Portuguese, 9yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family 18

CasePresentingHPOs:

CaseHPOFreeText: mild central fundus changes, vision: 2/10 / 2/10

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, dHPLC

PreviouslyPublished: n/a

Variant: c.1804C<T/ c.32T>C(1); p.Arg602Thr/p.Leu11Pro

ClinVar: 99217

CAID: CA227106

SupplementalData: n/a

Case#: Maia-Lopes Family 17 Proband 5137, Portuguese, 25yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family 17

CasePresentingHPOs:

CaseHPOFreeText: moderate central fundus changes, vision: 3/10 / FC

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, dHPLC

PreviouslyPublished: n/a

Variant: ND / c.32T>C(1); ND/p.Leu11Pro

ClinVar: 99217

CAID: CA227106

SupplementalData: n/a

In supplemental table S2, Case LL291 is a female listed as "likely solved" with a clinical diagnosis of CRD. Proband is compound heterozygous for c.32T>C p.(Leu11Pro) and c.5196+1137G>A.

In Supplemental table S1, this proband is a female, 54yo at report, 50yo at onset. Nyctalopia, visual acuity=0.05/0.6, OD: extremely high myopia OS: high myopia, no family information

Supplementary table 2 lists this variant as previously reported in 3 individuals from PMID: 19365591

Case#: P3, male, 16yo at report, 9yo at dx, US with Indian ethnicity

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: BCVA (logMAR)= OD=20/160 (0.90), OS=20/125 (0.80)

CaseNotHPOs:

CaseNotHPOFreeText: ocular comorbidities such as diabetic retinopathy, uveitis, or glaucoma

GenotypingMethod: "genetic testing"

PreviouslyPublished: n/a

Variant: c.2453G>A; c.4532C>A (p.Pro1511His)

ClinVar: 99135

CAID: CA227000

SupplementalData: table 1

This variant is listed in supplementary tables S2 and S3. Proband KN-187 is a "solved" patient, meaning the phenotype matches the genotype. Compound heterozygous (c.6290C>T p.P2097L; c.6445C>T p.R2149X) male with Stargardt disease- all that is provided.

Case#: MD-0790, Spanish

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "STGD1 was determined according to initial symptoms of VA loss; fundus images showing orange-yellow flecks in the retina, a beaten-bronze appearance; and normal or cone-altered ffERG results"

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Index cases were studied by different next-generation sequencing (NGS) strategies, including targeted gene panels, clinical exome, and/or whole-exome sequencing

PreviouslyPublished: n/a

Variant: c.1715G>C p.(Arg572Pro); c.4918C>T p.(Arg1640Trp)

ClinVar: 99073

CAID: CA226919

SupplementalData: Table S1

This variant was found in homozygosity 3 times in table S1 (Families MD-0991, MD-1164, and MD-1302). All with a STGD1 phenotype.

MD-0991 had onset of VA loss at 25yo, cone-rod pattern on ERG, and BCVA was 1.2/1.2. Segregation was mentioned, but no details provided.

MD-1164 had onset of VA loss at 42yo, no VF loss, and BCVA was 0.2/0.3. Segregation was not mentioned.

MD-1302 had no clinical details available.

GenotypingMethod: Index cases were studied by different next-generation sequencing (NGS) strategies, including targeted gene panels, clinical exome, and/or whole-exome sequencing

【局限】研究采用独立样本而非追踪同一组受访者，这意味着结果反映的是人群层面的变化而非个体变化。这种方法无法捕捉个人使用习惯的演变，也无法确定用户增长是来自新用户还是现有用户增加使用频率。

【局限】模型无法追踪个体工人，只能提供粗略的就业市场变化图景，这一重要局限性意味着模型无法捕捉AI对特定人群的差异化影响，政策制定者需谨慎使用。

Supplemental Table 1. Patient WHP103 has this variant in compound heterozygosity with c.4720G>T(p.E1574*). Cannot confirm this is not the same proband as in PMID 31674661 since both have the same genotype and are of Chinese ancestry

Case#: QT959, Chinese

DiseaseAssertion: Cone-rod dystrophy

FamilyInfo: no pedigree provided for this family in this paper

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: 23776498-more phenotype information available there

Variant: c.[1957C > T];[4605insT] on WES

ClinVar: n/a

CAID: CA645372205

SupplementalData: n/a

PCMID:*PMC12657203

PMID41323838

Gene: ABCA4

HGNC ID: 34

Case#:80 year old man,

DiseaseAssertion:NA

FamilyInfo:NA

CasePresentingHPOs:NA

CaseHPOFreeText:Diagnosed w/ targardt disease at the age of 18 years, medical retierment at 64 as result

CaseNotHPOs:*parkinsons at 80

CaseNotHPOFreeText:NA

Genotyping Method:NA

PreviouslyPublished:NA

Variant:after gentic testing (unspecified) a pathogenic heterozygous mutation (G1961E) in ABCA4 gene a substiution, GAA) at amino acid position 1961, or c.5882 G>A at the complementary DNA level, or pGly1961Glu or G1961E at the protein level. No second mutation was identified. One of his 2 sisters had the same mutation.

ClinVar:NA

CAID:NA

SupplementalData:this goes into how eye retina transplant results and outcomes.

PMID: 28600779

Gene: ABCA4

HGNCID: HGNC:34

MonDO:

Case: 16N-0520, Male, Saudi Arabia, 1 yo

DiseaseAssertion:

FamilyInfo: Consanguineous parents, positive family history

CasePresentingHPOs: HP:0000618, HP:0000648 (Blindness, Optic atrophy)

CaseHPOFreeText: Coloboma of eye

GenotypingMethod: WES, analysis of Vision Panel, constituent genes are described in PMID 26112015.

SupplementalData: Supplemental table

Variant: ABCA4:NM_000350:exon49:c.6764G>T:p.S2255I

CAID: CA202970

gnomAD: 0.4845 (gnomAD v4.0.0, Grpmax Filtered AF African/African-American) https://gnomad.broadinstitute.org/variant/1-93996161-C-A?dataset=gnomad_r4

VariantEvidence: Authors classified as VOUS. But later downgraded to LB in PMID 31130284.

Case#: Case #3483, likely European, 10yo at onset

DiseaseAssertion: ABCA4 disease

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: foveal sparing

GenotypingMethod: NGS, Sanger

PreviouslyPublished: n/a

Variant: c.2453G>A (p.Gly818Glu); c.4462T>C (p.Cys1488Arg)

ClinVar: 99135

CAID: CA227000

SupplementalData: supplemental table 1

Case#: STGD47/164, 10-14yo at onset, German

DiseaseAssertion: STGD

FamilyInfo: segregation in family

CasePresentingHPOs:

CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

PreviouslyPublished: n/a

Variant: IVS13+1G→A; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

ClinVar: 7879

CAID: CA119128

SupplementalData: n/a

This variant was found in 2 control alleles. No additional details

Case#: Patients #33 and 34, female, 63 and 61yo at report, respectively, German

DiseaseAssertion: ABCA4-related retinopathy

FamilyInfo: n/a but they could be related

CasePresentingHPOs:

CaseHPOFreeText: "Inclusion criteria comprised the presence of at least one disease-causing mutation in ABCA4 and a phenotype consistent with ABCA4-related retinopathy, including RPE atrophy and flecks." BCVA [LogMAR] for patient #33: OD= 0.4, OS= 0.1. BCVA [LogMAR] for patient #34: OD= 1.5, OS= 1.0. Reduced (over 2 SD) photopic B-wave and 30-Hz flicker amplitudes

CaseNotHPOs:

CaseNotHPOFreeText: Insufficient pupil dilation, additional retinal pathology, previous vitreoretinal surgery, or other ocular comorbidities substantially affecting visual function (e.g., significant media opacity, amblyopia, or optic nerve disease) led to exclusion. Abnormal responses on scotopic and photopic full-field ERG

GenotypingMethod:

PreviouslyPublished: likely the same patients as other Muller papers in this curation

Variant: c.3468C>G p.(Tyr1156*) and c.5059A>T p.(Ile1687Phe)

ClinVar: n/a

CAID: CA341290648

SupplementalData: Table S1 has genotype/phenotype info for probands

Case#: Sporadic Case #15, Mexican

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosis based on: "onset of symptoms in childhood or early adulthood (before 20 years of age), bilateral central vision loss (central and peripheral visual field computerized testing), a retinal “beaten-bronze” foveal appearance and/or yellow-whitish flecks from the posterior pole to the mid periphery, normal caliber of the retinal vessels, no pigmented bone spicules in the retinal periphery, a normal to subnormal electroretinogram, and a typical dark choroid in fluorescein angiography."

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: allele 1: c.6221G>T (p.G2074V) allele 2: c.2453G>A (p. G818E); direct sequencing of exons of ABCA4

ClinVar: 99135

CAID: CA227000

SupplementalData: n/a