Supplementary Table S6—Probands harbouring putative variants with incomplete penetrance;
This variant was found in Patient 074752 in cis with a nonsense (c.6088C>T) and in trans with an intronic variant (c.4253+43G>A); neither of which has been curated yet by the ABCA4 VCEP
W663X
Not sure if this variant is c.1988G>A or c.1989G>A.
Supplementary TableS10
This variant is listed for Stargardt DNAID#067322 in trans with c.5603A>T p.(Asn1868Ile). No phenotype information provided.
The proband (Patient #20
Case#: Female, family #5, Patient #20
DiseaseAssertion: STGD
FamilyInfo: Proband's sister presented with same clinical prognosis. Sister diagnosed with pattern dystrophy and photoaversion at age 57, with difficulty seeing at night. Sister has nuclear sclerotic and cortical cataracts in both eyes.
CasePresentingHPOs: HP:0000662, HP:0000603, HP:0000603, HP:0000493
CaseHPOFreeText: Proband presented with localized blur at age 62, (late onset) in her left eye. BVCA 20/20-3 and 20/20-2 at age 70. Also has macular lesions with stage 2 fundus flecks.
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.
PreviouslyPublished: n/a
Variant: p.N18681, IVS36:c.5196+1G>A
ClinVar: M2) 99067, M6) 99351
CAID: N/A
SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom
F17-003
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.[1622T>C;3113C>T]
ClinVar: 99067, 7894
CAID: n/a
gnomeAD 0.0001266 allele frequency
SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.
4.4. Disease Course in Patients Harbouring p.(Gly1961Glu) or p.(Asn1868Ile) Allele
It is known that patients harbouring p.(Gly1961Glu) or p.(Asn1868Ile) allele share some common clinical characteristics and present with a milder disease phenotype than patients carrying other alleles. A typical feature of patients with p.(Gly1961Glu) is BEM, which is otherwise present in around 20% of all STGD1 patients.
Sequencing of the coding region of ABCA4 and of the entire ABCA4 locus revealed one heterozygous ABCA4 variant c.3113C>T; p.(Ala1038Val). No other (likely) pathogenic coding or noncoding ABCA4 variants including copy number variants were identified.
ABCA4 variant revealed but not target of research and doesn't seem to amount to anything Variantc.3113C>T p.(Ala1038Val)