ClinVar Miner

Submissions for variant NM_000350.2(ABCA4):c.1622T>C (p.Leu541Pro) (rs61751392)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085410 SCV000692637 likely pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085410 SCV000225507 uncertain significance not provided 2016-11-16 criteria provided, single submitter clinical testing
GeneDx RCV000085410 SCV000577606 pathogenic not provided 2018-08-02 criteria provided, single submitter clinical testing The L541P pathogenic variant in the ABCA4 gene have been reported numerous times in association with autosomal recessive cone-rod dystrophy and Stargardt disease (Rivera et al., 2000; Briggs et al. et al., 2001; Webster et al., 2001; Braun et al., 2013). In the literature, these two variants (L541P and A1038V) often occur together on the same allele, in cis, representing a complex L541P/A1038V allele, which is considered to represent a German founder mutation (Rivera et al., 2000; Briggs et al., 2001; Webster et al., 2001; Wiszniewski et al., 2005). However, personal communication with an external gene expert revealed that the L541P and A1038V variants have been identified by her lab on opposite alleles (in trans). In addition, both the L541P and A1038V have been observed independently in trans with another pathogenic variant in individuals with Stargardt disease (Rivera et al., 2000; Briggs et al., 2001; Burke et al., 2012). Functional studies demonstrate that both the L541P/A1038V complex allele as well as the L541P and A1038V variants independently result in reduced ATPase activity; however, the affect of A1038V is milder compared to that of L541P alone or the L541P/A1038V complex allele (Sun et al., 2000; Wiszniewski et al., 2005; Zhang et al., 2015). We interpret L541P as a pathogenic variant when present independently or when occurring together in cis with A1038V, which this variant is most commonly seen with.
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408513 SCV000281824 pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000504750 SCV000926446 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787481 SCV000926447 likely pathogenic Stargardt disease 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787482 SCV000926448 likely pathogenic Macular dystrophy 2018-04-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases,University of Cambridge RCV000504750 SCV000598938 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases,University of Cambridge RCV000408513 SCV000598939 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases,University of Cambridge RCV000505133 SCV000598940 likely pathogenic Retinal dystrophy 2015-01-01 no assertion criteria provided research
Retina International RCV000085410 SCV000117547 not provided not provided no assertion provided not provided

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