ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.768G>T (p.Val256=) (rs62645944)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408540 SCV000281810 pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085866 SCV000329045 pathogenic not provided 2018-11-19 criteria provided, single submitter clinical testing The c.768 G>T variant has been previously reported in the literature in association withABCA4-related disorders (Maugeri et al., 1999; Roberts et al., 2012). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant damages the natural splice donor site of intron 6, which is expected to cause abnormal gene splicing. Functional studies have shown that the c.768 G>T variant results in low or absent mRNA expression (Maugeri et al., 1999). Therefore, we consider this variant to be pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085866 SCV000703956 pathogenic not provided 2016-12-09 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763049 SCV000893530 pathogenic Cone-rod dystrophy 3; Age-related macular degeneration 2; Stargardt disease 1; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000085866 SCV001210301 pathogenic not provided 2020-01-10 criteria provided, single submitter clinical testing This sequence change affects codon 256 of the ABCA4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ABCA4 protein. This variant is present in population databases (rs62645944, ExAC 0.02%). This variant has been observed in many individuals affected with Stargardt disease (PMID: 10090887, 23695285, 11726554, 15161829). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99505). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 10090887, 29162642). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074394 SCV001239973 pathogenic Retinal dystrophy 2019-08-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085866 SCV001247758 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Retina International RCV000085866 SCV000118009 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000408540 SCV000599025 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research
Human Genetics - Radboudumc,Radboudumc RCV000678516 SCV000804588 pathogenic Retinitis pigmentosa 19 2016-09-01 no assertion criteria provided clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787525 SCV000926493 likely pathogenic Macular dystrophy 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787526 SCV000926494 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research

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