ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5537T>C (p.Ile1846Thr)

gnomAD frequency: 0.00001  dbSNP: rs61750575
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000085737 SCV001582798 pathogenic not provided 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1846 of the ABCA4 protein (p.Ile1846Thr). This variant is present in population databases (rs61750575, gnomAD 0.006%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 10090887, 23143460, 28355279; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99383). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
3billion RCV003152681 SCV003842093 likely pathogenic Cone-rod dystrophy 3 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.95; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic (ClinVar ID: VCV000099383). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Retina International RCV000085737 SCV000117878 not provided not provided no assertion provided not provided

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