ClinVar Miner

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

gnomAD frequency: 0.00006  dbSNP: rs62645944
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Total submissions: 17
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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 Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085866 SCV000329045 pathogenic not provided 2021-11-16 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, specifically, the c.768 G>T variant results in low or absent mRNA expression (Maugeri et al., 1999); In silico analysis supports that this missense variant has a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 26261413, 15161829, 23695285, 28118664, 29925512, 31522899, 22968130, 19074458, 24453473, 22264887, 10090887, 22328824, 23891399, 28771251, 29310964, 31618761, 30903310, 32581362, 31589614, 29555955, 30718709, 29162642, 20647261)
Eurofins NTD LLC (GA) 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; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000085866 SCV001210301 pathogenic not provided 2021-12-13 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. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs62645944, gnomAD 0.02%). This variant has been observed in individual(s) with Stargardt disease (PMID: 10090887, 11726554, 15161829, 23695285). 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: 99505). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 10090887, 29162642). The resulting mRNA is expected to undergo nonsense-mediated decay. 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 Center for Human Genetics Tuebingen RCV000085866 SCV001247758 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV000408540 SCV001548123 likely pathogenic Severe early-childhood-onset retinal dystrophy 2021-01-30 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085866 SCV001905562 pathogenic not provided 2021-09-15 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 Severe early-childhood-onset retinal dystrophy 2015-01-01 no assertion criteria provided research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ 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
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000085866 SCV001959558 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000085866 SCV001966823 pathogenic not provided no assertion criteria provided clinical testing
PerkinElmer Genomics RCV000085866 SCV002019766 pathogenic not provided 2019-07-18 no assertion criteria provided clinical testing

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