ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.4577C>T (p.Thr1526Met) (rs61750152)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085656 SCV000229390 pathogenic not provided 2015-02-12 criteria provided, single submitter clinical testing
GeneDx RCV000085656 SCV000511899 pathogenic not provided 2018-05-18 criteria provided, single submitter clinical testing The T1526M variant in the ABCA4 gene has been reported previously in association with autosomal recessive ABCA4-related retinal dystrophies, including Stargardt disease and cone-rod dystrophy (Lewis et al., 1999; Cideciyan et al., 2009; Downes et al., 2012; Riveiro-Alvarez et al., 2013; Duncker et al., 2015). The T1526M variant is observed in 16/126,708 (0.012%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). The T1526M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Functional studies demonstrated that this variant results in reduced ATPase activity (Sun et al., 2000). We interpret T1526M as a pathogenic variant.
Ambry Genetics RCV000623715 SCV000742931 likely pathogenic Inborn genetic diseases 2017-10-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Invitae RCV000085656 SCV001200444 pathogenic not provided 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1526 of the ABCA4 protein (p.Thr1526Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs61750152, ExAC 0.01%). This variant has been observed to segregate with Stargardt disease in at least one family and has been observed in unrelated individuals affected with Stargardt disease or cone-rod dystrophy (PMID: 19074458, 9973280). ClinVar contains an entry for this variant (Variation ID: 99303). This variant has been reported to affect ABCA4 protein function (PMID: 11017087). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075849 SCV001241488 pathogenic Retinal dystrophy 2019-08-02 criteria provided, single submitter clinical testing
Retina International RCV000085656 SCV000117796 not provided not provided no assertion provided not provided
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000210286 SCV000259076 likely pathogenic Retinitis pigmentosa 19 2015-01-23 no assertion criteria provided clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000177509 SCV000598981 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002827 SCV001160844 pathogenic Stargardt disease 2019-06-23 no assertion criteria provided research

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