ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2915C>A (p.Thr972Asn)

dbSNP: rs61749451
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000085523 SCV001218249 pathogenic not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 972 of the ABCA4 protein (p.Thr972Asn). This variant is present in population databases (rs61749451, gnomAD 0.007%). This missense change has been observed in individual(s) with Stargardt disease or retinitis pigmentosa (PMID: 28041643, 28559085, 29925512). 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: 99174). 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.
Blueprint Genetics RCV000504717 SCV001240215 likely pathogenic Retinal dystrophy 2019-01-29 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000505078 SCV001950193 likely pathogenic Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Thr972Asn variant in ABCA4 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM1, PM2, PP1, PP3. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Fulgent Genetics, Fulgent Genetics RCV002498454 SCV002805465 pathogenic Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 2021-09-24 criteria provided, single submitter clinical testing
Retina International RCV000085523 SCV000117660 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505078 SCV000598954 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504717 SCV000598955 likely pathogenic Retinal dystrophy 2015-01-01 no assertion criteria provided research

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