This variant was not evaluated.

This variant was not evaluated.

This variant is found in table S2A to have an OR of 0 with a CI (0-0.02). PS4 not met

Case#: 7,554 Female

DiseaseAssertion: Retinitis Pigmentosa

FamilyInfo: autosomal recessive

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

Genotyping Method: Previous genotyping and NGS

PreviouslyPublished:

Variant: NM_000350.3:c.1554G>A

ClinVar: 3720226

CAID: CA418825668

SupplementalData:

PMID: 26992781

Gene: ABCA4

Disease: CRD

Case#: MD-0242, onset at 18yo, 24yo at report

DiseaseAssertion: STGD1

FamilyInfo: Segregation noted, but no specific details provided

CasePresentingHPOs:

CaseHPOFreeText: VA loss, BCVA=0.1/0.1, "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: VF loss, abnormal ERG

GenotypingMethod:

PreviouslyPublished: n/a

Variant: c.1715G>C p.(Arg572Pro); c.5242G>A p.(Gly1748Arg)

ClinVar: 99073

CAID: CA226919

SupplementalData: Table S1

PMID: 32619608

Gene: ABCA4

Disease: Stargardt disease (STGD1)

Case#: Patient #13

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: RPE atrophy (clearly demarcated definitely decreased fundus autofluorescence (FAF) under short-wavelength excitation light (488 nm) in combination with hypertransmission in optical coherence tomography (OCT)) areas ≥0.05 mm2 secondary to STGD1 or AMD. diagnosis of STGD1 was based on (1) a compatible phenotype (yellow-white flecks that correlated with hyperautofluorescent flecks on FAF imaging) and (2) the presence of at least one mutated ABCA4 allele as well as the absence of mutations in peripherin-2 (PRPH2). Minimum age of onset (first reported subjective symptoms) of 45 years.

CaseNotHPOs:

CaseNotHPOFreeText: Insufficient pupil dilation, additional retinal pathology, previous retinal treatment, or other ocular comorbidities substantially affecting visual function or image quality (e.g., significant media opacity, amblyopia or optic nerve disease) led to exclusion from the study. “diffuse-trickling geographic atrophy”

GenotypingMethod: Analysis of all coding exons of the ABCA4 and PRPH2 genes was done by either direct chain-terminating dideoxynucleotide Sanger sequencing, a custom-designed GeneChip CustomSeq Resequencing Array, or NGS

PreviouslyPublished: possible since the study was at the same university with the same first author as PMID: 33214501

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

ClinVar: n/a

CAID: CA341290648

SupplementalData: supplement 1 has the genotype for probands

PMID: 30140905

Gene: ABCA4

Disease: Stargardt disease, ARMD

Case#: STGD102, 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: R572Q-2588G→C IVS35+2T→A in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

ClinVar: 7900

CAID: CA226918

SupplementalData: n/a

Case#: STGD113, 20-24yo 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: L541P-A1038V; 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#: 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

PMID: 29376001

Gene: ABCA4

Disease: hereditary and inflammatory ocular disorders

Unable to open this type of file, but according to LOVD this paper contains this variant and it is not in the main text.

PMID: 29641573

Gene: ABCA4

Disease: retinitis pigmentosa

PMID: 33214501

Gene: ABCA4

Disease: ABCA4-Related Retinopathy

Annotating here since the full text is a PDF.

Case#: Family AR263 proband, male, US, 9yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: 3 generations, no other affected members in the pedigree

CasePresentingHPOs:

CaseHPOFreeText: The essential and defining features of STGD were (1) pedigrees with at least one living affected individual compatible with autosomal recessive inheritance; (2) an ophthalmoscopically characteristic retinal disorder in families with both parents living; (3) bilateral central visual loss with both “beaten metal” elliptical foveal dystrophy and temporal pallor of the optic discs, documented by retinal color photography, with or without yellow-pigment epithelial flecks in the macular and/or retinal “near periphery”; and (4) the characteristic fluorescein angiographic feature of a dark choroid (Blacharski 1988).

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6445C>T (p.Arg2149Ter); c.6079C>T (p.Leu2027Phe). Heteroduplex and SSCP analyses were used to screen the 50 exons of ABCA4

ClinVar: 99460

CAID: CA227404

SupplementalData: n/a

PMID: 30076350

Gene: ABCA4

Disease: ARMD/stargardt

PMID: 28118664

Gene: ABCA4

Disease: Stargardt

3 STGD patients have this variant but no specific clinical details (supplemental table s5).

Patient 79: c.1654G>A p.(V552I); c.5196+1013A>G

Patient 265: c.1654G>A p.(V552I) only

Patient 320: c.1654G>A p.(V552I); c.4254-1G>C; c.6230G>A p.(R2077Q)

RT-PCR of midigenes demonstrated that this variant impacts splicing by causing a deletion (r.5461_5714del) which is predicted to result in a frameshift (p.Thr1821Aspfs*6). This variant showed 0% correctly spliced ABCA4 mRNA. This frameshift variant introduces a premature stop codon between codons 1-2255 (PVS1(RNA); 29162642). There do appear to be alternative splice products (supplemental figure s2), where exon 39 or 40, or both 39 and 40, are skipped, but in all cases, this leads to a frameshift.

PMID: 29162642 Gene: ABCA4 HGNC ID: 34

annotating here since the article is a PDF

Case#: Duno Patient D015, Danish

DiseaseAssertion: Stargardt flavimaculatus phenotype

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: The diagnosis was based on standard ophthalmological examinations including fundus photography, colour vision assessment, dark adaptometry, and full field ERG.

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCA4 mutation microarray and High-resolution melting (HRM) in patients in whom the array analysis identified either a heterozygous mutation (n = 50) or no mutation (n = 30).

PreviouslyPublished: n/a

Variant: c.1654G>A p.V552I; c.6478A>G p.K2160E; c.3380G>A p.G1127E phase unknown

CAID: CA239745

SupplementalData:

Case#: Muller Subject #8, 34yo, qAF=590

DiseaseAssertion: ABCA4-related retinopathy

FamilyInfo: mother was 59yo at report with qAF=399

CasePresentingHPOs:

CaseHPOFreeText: "ABCA4-related retinopathy was diagnosed based on characteristic findings on indirect ophthalmoscopy, optical coherence tomography, and conventional fundus AF imaging. The clinical diagnosis was confirmed by the presence of biallelic mutations in ABCA4, and segregation analysis was carried out with samples of the parents."

CaseNotHPOs:

CaseNotHPOFreeText: age ≥ 65 years, ethnicity other than Caucasian, significant lens opacities, dilated pupil diameter below 7 mm, unstable fixation, refractive error > ±6 diopters (spherical equivalent), and any other additional known ocular pathology or prior intraocular surgery.

GenotypingMethod: ABCA4 sequence analysis of all coding exons and flanking splice junctions was performed either by Sanger chain-terminating dideoxynucleotide sequencing after PCR amplification, by multiplex ligation-dependent probe amplification (MLPA) analysis (performed when only a single mutation was detected), or by next-generation sequencing (NGS) including a quantitative readout to detect large structural rearrangements using a gene panel covering 120 genes associated with inherited retinal disease as described previously.23 Validation of identified putatively pathogenic variants and segregation analysis were carried out by conventional sequencing

PreviouslyPublished: n/a

Variant: maternal allele: [c.1622T>C (p.Leu541Pro); c.3113C>T (p.Ala1038Val)]; paternal allele: c.1654G>A (p.Val552Ile); c.4771G>A (p.Gly1591Arg)

CAID: CA239745

SupplementalData:

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#: Case 4, Sex: Female, Age:34

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: Text mentions BCVA 20/100 in both eyes later became 20/240. Bilateral atrophic-appearing foveal lesions associated with yellowish-white fundus flecks at the posterior pole. Subnormal scotopic and photopic responses. Subretinal fibrosis in left eye. Hypofluorescence due to hyperplasia of RPE in left eye.

CaseNotHPOs:n/a

CaseNotHPOFreeText: No ocular trauma.

Genotyping Method: genetic analysis

PreviouslyPublished: n/a

Variant: Variant is a heterozygous mutation given as NM_000350.3(ABCA4):c.3113C>T (p.Ala1038Val)

ClinVar: Variation ID: 7894

CAID: CA119135

SupplementalData: n/a

Case#: Case 2, Sex: Male, Age:20

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs: HP:0007663, HP:0007401

CaseHPOFreeText: Text mentions visual acuity of 20/32 in right eye and 20/50 in left eye but later degrades to 20/200 in both eyes. pigmented changes in macula associated with flecks. Area of subretinal fibrosis in right eye. Subnormal scotopic and photopic responses. Instable fixation in both eyes with low retinal mean sensitivity. Hypofluorescent central area corresponding to macular atrophy and corresponding to flecks. Atrophic areas, some with pigment, localized in the temporal sector of the left eye which have become areas of subretinal fibrosis.

CaseNotHPOs:n/a

CaseNotHPOFreeText: Anterior segment showed a healthy ocular adnexa, and specular, transparent and 'in situ' lens, absence of any ocular trauma.

Genotyping Method: genetic analysis

PreviouslyPublished: n/a

Variant: Variant is a homozygous mutation given as NM_000350.3(ABCA4):c.571-2A>T

ClinVar: Variation ID: 1048133

CAID: CA958800

SupplementalData: n/a

PMID:23341817

Gene: ABCA4

HGNC ID: 34

Case#: 25 year old Female, Sikh, India, Punjab

DiseaseAssertion: EORSD

FamilyInfo: Family history for other disease were negative

CasePresentingHPOs: HP:0007401, HP:0007913

CaseHPOFreeText: Macular atrophy, scar and pigment OU, plus midperipheral pigmentation OU

CaseNotHPOs: N/a

CaseNotHPOFreeText: N/a

Genotyping Method: BGISeq-500 2 x 100-bp paired-end module, Burrows-Wheeler Aligner and Genome Analysis Tooklit HaploptypeCaller

PreviouslyPublished: N/a

Variant: NM_000350.3(ABCA4):c.6729+5_6729+19del

ClinVar: 283573

CAID: CA501163

SupplementalData: Family reported never saw well and had poor vision and nystagmus before the age of one.

Case#: German/British, 76

DiseaseAssertion: EOSRD

FamilyInfo: Grandparents from Germany and the United Kingdom

CasePresentingHPOs: HP:0007401, HP:0007913

CaseHPOFreeText: Macular atrophy and pigmentation, peripheral pigmentation, early-onset severe retinal dystrophy

CaseNotHPOs: N/a

CaseNotHPOFreeText: N/a

Genotyping Method: BGISeq-500 2 x 100-bp paired-end module, Burrows-Wheeler Aligner and Genome Analysis Tooklit HaploptypeCaller

PreviouslyPublished: n/a

Variant: c.1622T>C, c.4326C>A, and c.3113C>T

ClinVar: 99067, 417991, 7894

CAID: CA226911, CA957653, CA119135

SupplementalData: The c.1622T>C variants and c.3133C>T are thought to be same gene copy

PMID: 38309476

Gene: ABCA4

Disease: ABCA4-Associated Retinal Disease

Case#: Proband P399, Family F345, male, 8yo at onset, US

DiseaseAssertion:

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: phenotypically focused tiered testing strategy beginning with allele-specific testing of the most common disease alleles and progressing through Sanger sequencing of candidate genes and, in many cases, to next generation sequencing of whole exomes and whole genomes

PreviouslyPublished: n/a

Variant: Pro1380Leu (c.4139C>T); Glu2031Lys (c.6091G>A) phase unconfirmed

ClinVar: 866538

CAID: CA341279017

SupplementalData: table s2 (listed as table 1 when you open it)

PMID: 37217489

Gene: ABCA4

Disease: macular dystrophy

Case#: Patient 339, Argentinian

DiseaseAssertion: macular dystrophy

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6383A>G (p.His2128Arg); c.4457C>T (p.Pro1486Leu) NGS

ClinVar: 99455

CAID: CA227399

SupplementalData: supplemental table 1 contains phenotype info

PMID: 24550365

Gene: ABCA4

Disease: Retinal Degenerations

previously reported in PMID: 26377081

PMID: 33899203

Gene: ABCA4

HGNC ID: 34

Case#: Case1, Sex:Male, Age:19

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: Clinical Notes: Peripapillary sparing, discrete flecks; nummular atrophy. General notes: Panretinal cone dysfunction with preserved rod function was documented by ERG

CaseNotHPOs:n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Whole exome sequencing data generation. Additional sequencing targeted amplification fo PRPH2 and ELOVL4 using PCR.

PreviouslyPublished: n/a

Variant: Variant 1 given as p.N965S; NM_000350.3(ABCA4):c.2894A>G (p.Asn965Ser). Variant 2 given as p.R2038W; NM_000350.3(ABCA4):c.6112C>T (p.Arg2038Trp)

ClinVar: Variation ID: 236096; Variation ID: 99430

CAID: CA958124; CA227368

SupplementalData: Proband variant information given in Table 1.

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

c.1989G>CA (p.Trp663Ter) 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

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

PMID: 10612508

Gene: ABCA4

Case#: Patient 1, 40-year-old female

DiseaseAssertion: STGD1

FamilyInfo: One of four affected siblings in a family of eight. Segregation consistent with autosomal recessive inheritance.

CasePresentingHPOs: HP:0000545 — Decreased visual acuity HP:0000612 — Central scotoma HP:0007754 — Macular atrophy HP:0030638 — Retinal flecks HP:0000512 — Abnormal fundus morphology

CaseHPOFreeText: Progressive decline in visual acuity since age 15. Best-corrected visual acuity RE 20/400, LE 20/150. Central scotomas reported. Fundus exam showed bilateral central macular atrophy (worse in right eye), pigment deposits at the level of the retinal pigment epithelium, and numerous yellow flecks in the midperiphery. Fluorescein angiography demonstrated central hypofluorescence corresponding to atrophy with surrounding hyperfluorescence and peripheral dark choroid.

CaseNotHPOs: HP:0000662 — Night blindness (absent)

CaseNotHPOFreeText: Patient denied nyctalopia.

GenotypingMethod: PCR amplification and direct sequencing of all 50 exons of ABCA4 following SSCP screening.

PreviouslyPublished: Yes

Variant: NM_000350.2:c.2588G>C (p.Gly863Ala) NM_000350.2:c.161G>A (p.Cys54Tyr)

ClinVar: Not reported

CAID: Not reported

SupplementalData: Segregation demonstrated in pedigree (Figure 1); mutation confirmation by sequencing (Figure 4)

PMID: 10612508

Gene: ABCA4

HGNC ID: 34

Case#: Patient 8 yo, F, Turkiye, onset at 8yo (early onset)

DiseaseAssertion:STGD1

FamilyInfo: no consanguinity between parents, neither parents are affected or show symptoms

CasePresentingHPOs: HP:0008035, HP:0011504

CaseHPOFreeText: vision of 6/10

CaseNotHPOs: HP:0000007, HP:0000608

CaseNotHPOFreeText: normal movements and mobility, unremarkable slit-lamp, no fundoscopy changes, unremarkable OCT

Genotyping Method: N/A

PreviouslyPublished: N/A

Variant: NM_000350.3a: c.3322C>T,p.(Arg1108Cys)rs61750120

CAID: CA220683

SupplementalData: N/A

PMID: 33633436 Gene:ABCA4 HGNC:34

Case:RP3,03, male proband with first symptoms as 18 years old. DiseaseAssertion:RP19 FamilyInfo:Proband was born in a consangiuineous family of Moroccan origin. Parents were unaffected. InheritancePattern:AutosomalRecessive CasePresentingHPOs:HP:0007994,HP:0000510,HP:0100014 CaseHPOFreeText:Difficulty with dark adaptation, Fig 4B severe impairment of the entire visual field. Fig 4A Scotopic and photopic ERG traces were altered indicating rod and cone photoreceptor dysfunctions. Macular OCT showed relative preservation of the foveal structure. Epiretinal membrane formation was observed. CaseNOTHPOs:HP:0007667 CaseNOTHPOFreeText:absence of cystic spaces CasePreviousTesting: GenotypingMethod:Whole exome sequencing MultipleGeneVariants: compound heterozygous GeneName:ABCA4 Variant:NM_000350.3(ABCA4):c.5908C>T (p.Leu1970Phe) ClinVarID :7892 gnomAD:0.00362 GeneName:ABCA4 Variant:NM_000350.3(ABCA4):c.6148G>C (p.Val2050Leu) ClinVarID :7884 gnomAD:0.00308

PMID: PMC7883928

Gene: ABCA4

HGNC ID: 34

Case#: Sporadic Case #4, 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.1804C>T (p.R602W) and c.2828G>A (p.R943Q) allele 2: c.2453G>A (p. G818E); direct sequencing of exons of ABCA4

ClinVar: 99135

CAID: CA227000

SupplementalData: n/a

Case#: Familial Case #8, 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) allele 2: c.4249_4251 delTTC (p.F1417del); direct sequencing of exons of ABCA4

ClinVar: 99135

CAID: CA227000

SupplementalData: n/a

Case#: Sporadic Case #10, 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: c.2453G>A (p. G818E) homozygous; direct sequencing of exons of ABCA4

ClinVar: 99135

CAID: CA227000

SupplementalData: n/a

PMID:32043016

Gene: ABCA4

HGNC ID: 34

PMID: 24695063

Gene: ABCA4

Disease: Stargardt

Case#: Patient 10, female, Lithuanian, onset at 6yo

DiseaseAssertion: STGD

FamilyInfo:Both parents and older brother healthy; no clinical signs in grandparents or extended family; inheritance most likely autosomal recessive

CasePresentingHPOs: HP:0000505, HP:0012508, HP:0001105, HP:0025148, HP:0000662

CaseHPOFreeText: progressive central vision loss from age 6; visual acuity dropped from OD=0.3, OS=0.3 to OD=0.08, OS=0.1 over 4 years; fundus examination: yellow pisciform flecks at the maculae; OCT: thin atrophic neurosensory retina in foveal region, altered photoreceptor reflectivity, thinner RPE; ERG: loss of scotopic b-waves, attenuated scotopic a-wave, missing oscillatory potentials, loss of photopic a- and b-waves; “bull’s eye” maculopathy noted

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: RetChip v1.0 STGD-module array and confirmation by Sanger sequencing

PreviouslyPublished: n/a

Variant: ABCA4 NM_000350.2 c.1622T>C p.(L541P), NM_000350.2 c.3113C>T p.(A1038V)

CAID: CA226911, CA119135

SupplementalData: clinical images, OCT, ERG, and pedigree information included in supplemental data (Figs. 1–5)

Case#: Family MD-0560 Proband, 16yo 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 electroretinogram (ERGs)." VA loss, VF loss, BCVA=0.1/0.1

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

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

ClinVar: 2202779; 99224

CAID: CA341277358; CA227116

SupplementalData:

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:

PMID: 28446513

Gene: ABCA4

Disease: ABCA4 disease

PMID: 19959634

Gene: ABCA4

Disease: Stargardt

Case#: Family MD-0084/ARDM-84 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: n/a

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

ClinVar: 2202779

CAID: CA341277358

SupplementalData: n/a

This variant was found in 6 different families (F32, F33, F40, F41, F42, and F43).

PP4: F32: Patient #37 is a 31yo male, ADI=4yo, dx of CRD F33: Patient #38 is a 32yo female, ADI=>32yo, dx of STGD, segregation in the family but no further details F40: Patient #45 is a 65yo male, ADI=26yo, dx of CRD, segregation of homozygous alleles with disease was demonstrated in 2 affected siblings in Family 40. F41: Patient #46 is a 38yo female, ADI=>38yo, dx of STGD F42: Patient #47 is a 45yo female, ADI=>53yo, dx of STGD F43: Patient #48 is a 55yo female, ADI=46yo, dx of STGD

PM3: In family 40, the proband was homozygous. In the other families, the variant was in compound heterozygosity with p.A1038V;p.L541P (F32); p.A1038V (F33); p.V1686M (F41); p.G1961E (F42); p.K2172R (F43).

Case#: Two affected sisters/Female siblings/Progressive onset initially presenting as Stargardt disease

DiseaseAssertion: ABCA4

FamilyInfo: Large American family pedigree with two affected sisters. Both sisters were compound heterozygous for two novel ABCA4 variants. Unaffected relatives carried one variant or neither variant, supporting autosomal recessive inheritance.

CasePresentingHPOs: HP:0000556, HP:0000572, HP:0007754, HP:0000648, HP:0000510, HP:0001133, HP:0000610

CaseHPOFreeText: Proband initially showed phenotype compatible with Stargardt disease with progressive central vision loss. Over several years disease advanced into severe cone-rod dystrophy with worsening retinal degeneration, abnormal visual fields, and reduced electroretinography responses.

CaseNotHPOs: n/a

CaseNotHPOFreeText: Unaffected family members with only one mutation had no retinal disease phenotype.

Genotyping Method: Genome-wide linkage analysis using 408 microsatellite markers followed by direct Sanger DNA sequencing of all ABCA4 exons and exon-intron boundaries. Segregation analysis performed in family members.

PreviouslyPublished: No, both variants were novel at time of publication.

Variant: ABCA4 (RefSeq: NM_000350.3): c.655A>T ; ABCA4 (RefSeq: NM_000350.3): c.5312+3A>T

ClinVar: 632118

CAID: n/a

SupplementalData: Variants absent in 200 unrelated controls. Clinical testing included visual acuity, fundus examination, fluorescein angiography, visual field testing, and electroretinography. Compound heterozygous state associated with severe progressive phenotype.

Case#: Female, 54 yo

FamilyInfo: No family members were available

CasePresentingHPOs: HP:0007924, HP:0000519,HP:0001105, HP:0030825,

CaseHPOFreeText: diagnosed with HIV 15 years ago. She was initially diagnosed with HIV following recurrent respiratory infections and an unintentional weight loss of 12 kg over six months. The diagnosis was confirmed via a positive HIV antibody test, followed by a Western blot confirmation and a CD4 count of 400 cells/mm³ at the time of diagnosis. Antiretroviral therapy (ART) was initiated shortly after confirmation of the diagnosis. Her condition has since progressed to AIDS, with a recent CD4 count of 80 cells/mm³. She was on ART, including tenofovir, emtricitabine, and efavirenz.

CaseNotHPOs: n/a

GenotypeMethod: NGS, Sanger Sequencing

Variant: c.2588G>C in exon 13, c.5461-10T>C in intron 39

ClinVar: Not reported in ClinVar

**SupplementalData: ** indicative of significant loss of central retinal structure (Figure 4).

This variant was transfected into HEK 293 cells and appears to show reduced expression and ATP-binding capacity, but no quantities were provided

In HEK293 cells, G863A was purified, reconstituted into membranes, and tested for basal and retinal-stimulated ATPase activities. G863A was shown to have reduced basal and retinal-stimulated ATPase (Fig 4d)

This variant was transfected into HEK 293 cells and appears to show reduced expression and ATP-binding capacity, but no quantities were provided

PMID: 10958761

Gene: ABCA4

Disease: Autosomal Recessive Cone-Rod Dystrophy

Case Annotation Template

Case#: Patient 2, female, age 62

DiseaseAssertion: STGD

FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: n/a

PreviouslyPublished: n/a

Variant: ENST00000370225.4:c.1222C>T

ClinVar: NM_000350.3(ABCA4):c.1222C>T (p.Arg408Ter)

CAID: CA179692

SupplementalData: composite mask analysis shown in figure 3 for patient 2, "Both patient 2 and 14 show foveal preservation of IS/OS and RPE," "Patients 2, 19, and 11 show large areas of matched degeneration and isolated IS/OS loss, "

Case#: Patient 10, female, age 19

DiseaseAssertion: STGD

FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: n/a

PreviouslyPublished: n/a

Variant: Allele 1: NM_000350.3:c.2588G>C Allele 2: NM_000350.3:c.1222C>T

ClinVar: Allele 1: NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala) Allele 2: NM_000350.3(ABCA4):c.1222C>T (p.Arg408Ter)

CAID: Allele 1: CA119128 Allele 2: CA179692

SupplementalData: composite mask analysis shown in figure 3 for patient 10

PMID: 30771335

Gene: ABCA4

HGNC ID: 34

This variant is found in compound heterozygosity with c.950del p.(Gly317Alafs*57) in family RP-0298 in this study. Proband is 10yo at onset of VA loss and VF loss, 8yo at night blindness, and 36yo at opthalmological exam. BCVA=HM/HM.

This variant is found in compound heterozygosity with c.2023G>A p.(Val675Ile) in family MD-1146 in this study. Proband is 46yo at onset of VA loss. 46yo at opthalmological exam. Normal ERG. BCVA=1/1. Not eligible for PP4 due to age of onset.

This variant is found in compound heterozygosity with c.4253+43G>A p.[=, Ile1377Hisfs*3] in family MD-0740 in this study. Proband is 61yo at onset of VA loss with no VF loss. 62yo at opthalmological exam. Cone pattern on ERG. BCVA=0.8/0.16. Not eligible for PP4 due to age of onset.

This variant is found in compound heterozygosity with c.3386G>T p.(Arg1129Leu) in family MD-0560 in a previous publication (PMID: 23755871)

Case#: Family ARDM-133 Proband, Spanish Retinal Dystrophy Investigation Network (EsRetNet), 8yo at onset, 42yo at report

DiseaseAssertion: arCRD

FamilyInfo: cosegregates

CasePresentingHPOs: HP:0007663, HP:0000575, HP:0007641, HP:0000613

CaseHPOFreeText: "The diagnosis of CRD was based on the following criteria: initial complaints of blurred central vision without a history of night blindness, poor visual acuity (typically 20/100 or worse, with progressive decline from an early age), impairment of color vision, funduscopic evidence of atrophic macular degeneration, peripheral disturbances including pigment clumping and/or pigment epithelial thinning, and greater or earlier loss of cone than rod ERG amplitude."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, PCR amplification

PreviouslyPublished: n/a

Variant: 32T→C, L11P; 2888delG

ClinVar: 99217

CAID: CA227106

SupplementalData:

PMID: 31212395

Gene: ABCA4

Disease: Stargardt disease

unable to access full text

PMID: 37498587

Gene: ABCA4

Disease: ABCA4-Associated Retinopathy

Proband can genotype and some phenotype information can be found in eTable 1.

Case#: Patient 601691#46, male, Italian, 32yo

DiseaseAssertion: ABCA4-Associated Retinopathy

GenotypingMethod: sequencing with Illumina NexSeq500 platform, confirmation with Sanger sequencing

PreviouslyPublished: n/a

Variant: c.5018+2T>C; c.6415C>T (p.Arg2139Trp)

CAID: CA227402

SupplementalData: eTable 1

PMID: 10206579

Gene: ABCA4

Disease: Stargardt dystrophy

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:

Looked through supplemental files and was unable to locate the patient from the LOVD entry for this variant for more phenotype details.

This variant is mentioned for patient 5 but is likely the same proband as in PMID: 19074458 since this is the same first author and same genotype

annotating here since unable to annotate on PDF.

Case#: Stargardt patient 22, Italian

DiseaseAssertion: STGD

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: STGD criteria: "(1) juvenile to adult onset of symptoms; (2) bilateral central vision loss; (3) macular dystrophy and/or atrophy (beaten bronze appearance or large patch of atrophy); (4) normal caliber of retinal vessels; (5) absence of pigmented bone spicules. The presence of yellow-white flecks was not considered obligatory inclusion criteria, even though they could be found in most of the patients of our series. Similarly, the possible presence of the “dark choroid” phenomenon could be identified in the fluorescein angiography examinations carried out on some patients in previous clinical settings, but it was not considered significant for the recruitment."

CaseNotHPOs:

CaseNotHPOFreeText: "myopia >6 diopters, hyperopia and astigmatism >3 diopters, ocular disorders other than RP, STGD, or AMD, significant systemic diseases, a history of inflammation-associated diseases and media opacities preventing fundus examination"

GenotypingMethod: all coding exons, including intron-exon boundaries of the ABCA4 gene (NM 000350) were sequenced. PCR

PreviouslyPublished: n/a

Variant: c.5882G>A (p.Gly1961Glu); c.4450C>T (p.Pro1484Ser); c.203C>T (p.Pro68Leu)

ClinVar: 99113

CAID: CA226972

SupplementalData: Table S2

PMID: 30285522

Gene: ABCA4

Disease: Stargardt disease

unavailable publicly, accessed through UNC library

MonDO: MONDO:0019353

Case: Family SG-04 Patient II:1. Indian Male, 26 years old diagnosed with Stargardt's disease DiseaseAssertion: Stargardt disease

FamilyInfo: Only child of nonconsanguineous parents. Proband's unaffected mother (I:1) harbored only one heterozygous variant (p.Gly1961Glu) in ABCA4. His father (I:2) was clinically normal and was not included for genetic testing.

CasePresentingHPOs: HP:0001129, HP:0007401 (Large central visual field defect, Macular atrophy)

CaseHPOFreeText: atrophic macular lesions

CaseNOTHPOs: HP:0011507 (macular flecks)

CasePreviousTesting: Five clinically confirmed unrelated patients with Stargardt disease and their available family members were enrolled for genetic analysis. Study subjects underwent a complete ophthalmic examination including measurement of visual acuity, intraocular pressure, slit lamp biomicroscopy, detailed fundus examination, fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT), and full field electroretinography (ERG). Fifty normal controls without any history of eye diseases were included.

GenotypingMethod: NGS panel testing targeting 184 genes with previously known pathogenic variations associated with multiple eye disorders. Peripheral blood samples were obtained from all subjects.

MultipleGeneVariants:

(1) GeneName: ABCA4

(1) Variant: p.Gly1961Glu

(1) CAID: CA119132

(1) gnomAD: The total minor allele frequency in gnomAD v4.1.0 is 0.003406 (5498/1614012 alleles).

(2) GeneName: ABCA4

(2) Variant: p.Tyr872X

(2) CAID: CA341276149

(2) gnomAD: Not found in gnomad v. 4.1

PMID: 38694055 Gene: ABCA4

This variant is listed in supplementary tables S2 and S3. Proband TM-319 is a "solved" patient, meaning the phenotype matches the genotype. Compound heterozygous (c.5318C>T p.A1773V) female with Stargardt disease- all that is provided.

Case#: Braun Family 6 Proband (from left to right, top to bottom of available pedigrees), male

DiseaseAssertion: Stargardt

FamilyInfo: Genotypes not provided for parents. No siblings

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.454C>T (p.R152X)

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

PMID: 19365591

Gene: ABCA4

Disease: Stargardt

Case#: Maia-Lopes Family 5 Proband 4514, Portuguese, 12yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family 5

CasePresentingHPOs:

CaseHPOFreeText: severe central fundus changes, vision: 1/10 / 1/10

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, dHPLC

PreviouslyPublished: n/a

Variant: c.32T>C(1) / c.[1A>G(1)]+[6089G>A(44)]; p.Leu11Pro/p.(Met1Val)+(Arg2030Gln)

ClinVar: 99217

CAID: CA227106

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#: Proband RPN-290, Male, 43yo at genetic testing, 27yo at dx, onset in 30s, Spanish

DiseaseAssertion: Nonsyndromic Inherited Retinal Dystrophies. Stargardt

FamilyInfo: Family RPN-133

CasePresentingHPOs:

CaseHPOFreeText: decreased visual acuity, photophobia, BCVA (logMAR) 28y: 0,0/0,0 35y: 0,4/0,1 43y: 1,0/1,0, central scotoma (56/ 63), yellow-white deposits around the macula, central and peripheral neuroepithelium thinning; 43y: without significant changes, 27y: normal visual evoked potentials, normal : full field electroretinography, abnormal electrooculogram (Arden index); 36y: delayed latency right eye visual evoked potentials, decreased cone and rod ffERG.

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS; MLPA and array CGH

PreviouslyPublished: n/a

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

ClinVar: 99283

CAID: CA227192

SupplementalData: supplemental table S2 has phenotype, S4 and S5 have genotype information

PMID: 37648803

Gene: ABCA4

Disease: retinitis pigmentosa

PMID: 37510299 Gene: ABCA4 CAID: CA119132

Case #: Eldest sister/Female/Onset at 3yo

DiseaseAssertion: SLC26A2

FamilyInfo: Family pedigree showing consanguinity of the proband's parents. The osteochondrodysplasia genotype, derived from a homozygous variant in the SLC26A2 gene and compound heterozygous variants in the ABCA4 gene, is responsible for the retinal phenotype

CasePresentingHPOs: HP:0034345, HP:0000556, HP:0002098, HP:0001903, HP:0001385, HP:0007754, HP:0002650, HP:0000939, HP:0025388, HP:0007987, HP:0003124, HP:0007401

CaseHPOFreeText: Visual acuity was 1/50 and 2/50 for both eyes, knee dysplasia, sticky platelet syndrome type II

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

GenotypyingMethod: genetic screening by next‐generation sequencing (NGS) was performed on a panel of genes involved in retinal dystrophy and macular degeneration

PreviouslyPublished: n/a

Variant: ABCA4 (RefSeq: NM_000350.3(ABCA4):c.203C>T (p.Pro68Leu))

CAID: n/a

SupplementalData: Comparison of phenotypes (table 1)

Case#: Patient 231, Female, age of onset at 7 y.o, Poland

DiseaseAssertion: STGD1

FamilyInfo: Mother was a carrier, unaffected father.

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158

CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.

Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.

PreviouslyPublished: yes

Variant: c.4234C>T , p.(Gln1412*)

ClinVar: 99263

gnomeAD 0.00001984 allelic frequency

CAID: n/a

SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.

Case#: Patient 225, Female, age of onset 7 y.o, Poland

DiseaseAssertion: STGD-1

FamilyInfo: no given family information.

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158

CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.

Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.

PreviouslyPublished: yes

Variant: c.634C>T,p.(Arg212Cys)

ClinVar: 7898

CAID: n/a

gnomeAD 0.0001177 allele frequency

SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.

Case#: Patient 231, Female, age of onset at 7 y.o, Poland

DiseaseAssertion: STGD1

FamilyInfo: Mother was a carrier, unaffected father.

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158

CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.

Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.

PreviouslyPublished: yes

Variant: c.5882G>A

ClinVar:7888

gnomeAD: 0.00310 allelic freq.

CAID: n/a

SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.

PMID: 26527198

Gene: ABCA4

HGNC ID: 34

Case#: 47-year-old female, sibling of patient 1.

DiseaseAssertion: Discordant STGD phenotype

FamilyInfo: The mother was found to harbour p.L541V/p.A1038V, and the father carried the p.R811C mutation; both of whom were asymptomatic with normal retinal examination (Fig. 1). ABCA4 screening detected three variants: two variants p.L541V and p.A1038V – commonly co-inherited in a complex allele in STGD (Maugeri et al. 2000) – and a third novel variant p.R881C (Fig. 1). Patient 1 had all three variants

CasePresentingHPOs: HP:0007401, HP:0025010, HP:0011507

CasePhenotypeFreeText: Patient 2 is the 47-year-old sister of patient 1. At initial examination in 1994, she reported a central scotoma. VA was 6/9 in both eyes with bilateral subtle foveal atrophy and perifoveal yellowish-white flecks (Fig. 1). By 2003, foveal atrophy had progressed with more perifoveal flecks (Fig. 1). In 2012, her VA was 6/12 bilaterally, but fundus findings remained stable (Fig. 1). AF imaging demonstrated a mottled signal within the central macula, optical coherence tomography showed outer retinal disruption confined to the central macula

CaseNotHPOs: N/A

CaseNotPhenotypeFreeText: N/A

CasePreviousTesting: The article mentions ABCA4 screen but does not go into detail. However, it does say,”(patient 2) harboured the complex allele (p.L541V/p.A1038V)”

GenotypingMethod: Again only mentioned ABCA4 screening without going into detail.

Variant: NM_000350.3:c.1621C>G and NM_000350.3(ABCA4):c.3113C>T

LegacyVariant: c.1621C>G (p.Leu541Val) and c.3113C>T(p.Ala1038Val)

CAID: CA341280463 and CA119135

gnomeAD: chr1-94063251-G-C and chr1-94043413-G-A

PreviouslyPublished: N/A

AdditionalInfo: Figure 1 provides information about the imaging of patients’ eyes that helps determine phenotype.

Case#: 80 yo M, siagonosed at 18 yo

DiseaseAssertion: Stargardt

FamilyInfo: one of his 2 sisters had same mutation to ABCA4

CasePresentingHPOs:,HP:0007663, HP:0008002

CaseHPOFreeText: RPE hyperplasia, atrophy of the inner and outer photoreceptor segments, the outer nuclear layer, and the outer plexiform layer, with scanty RPE cells in the macular area

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

Genotyping Method: N/A

PreviouslyPublished: none

Variant: G1961E

ClinVar: 7888

SupplementalData: See supplemental Material for further look at the probands Human Embryonic Stem Cell-derived Retinal Pigment Epithelium Transplantation