ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.3322C>T (p.Arg1108Cys) (rs61750120)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078665 SCV000110524 pathogenic not provided 2015-12-29 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000150052 SCV000281865 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000078665 SCV000490375 pathogenic not provided 2018-09-26 criteria provided, single submitter clinical testing The R1108C variant has been reported previously in association with autosomal recessive Stargardt disease in multiple unrelated individuals (Lewis et al.,1999; Rivera et al., 2000; Valverde et al., 2006). The R1108C variant is observed in 27/126,584 (0.0213%) alleles from individuals of non-Finnish European background in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). The R1108C 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-vitro functional studies demonstrate that R1108C has a damaging effect with characteristics of a defect in protein processing (Sabirzhanova et al., 2015). We interpret R1108C as a pathogenic variant.
Invitae RCV000078665 SCV001224349 pathogenic not provided 2020-01-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1108 of the ABCA4 protein (p.Arg1108Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs61750120, ExAC 0.02%). This variant has been observed in individual(s) with Stargardt disease and retinitis pigmentosa (PMID: 30337596, 26103963, 10958763, 11379881). 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: 92867). This variant has been reported to affect ABCA4 protein function (PMID: 26092729). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074904 SCV001240508 pathogenic Retinal dystrophy 2019-08-16 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000078665 SCV001249465 pathogenic not provided 2019-06-01 criteria provided, single submitter clinical testing
Retina International RCV000078665 SCV000117707 not provided not provided no assertion provided not provided
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002834 SCV001160852 pathogenic Stargardt disease 2019-06-23 no assertion criteria provided research

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