ClinVar Miner

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

gnomAD frequency: 0.00019  dbSNP: rs61750120
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) 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 Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000078665 SCV000490375 pathogenic not provided 2021-01-28 criteria provided, single submitter clinical testing Identified in association with autosomal recessive Stargardt disease in multiple unrelated individuals in published literature (Lewis et al.,1999; Rivera et al., 2000; Valverde et al., 2006) and in patients with Stargardt disease referred for genetic testing at GeneDx; Published functional studies demonstrate a damaging, temperature-sensitive processing effect on the ABCA4 protein (Sabirzhanova et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 11379881, 19074458, 24713488, 11702214, 26354092, 23757202, 11527935, 11726554, 11328725, 29555955, 28118664, 28559085, 29925512, 25283059, 16917483, 26092729, 23918662, 9781034, 10958763, 9973280, 26103963, 16703556, 30337596, 30653986, 31456290, 32845050, 32467599)
Invitae RCV000078665 SCV001224349 pathogenic not provided 2021-12-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1108 of the ABCA4 protein (p.Arg1108Cys). This variant is present in population databases (rs61750120, gnomAD 0.02%). This missense change has been observed in individual(s) with Stargardt disease and retinitis pigmentosa (PMID: 10958763, 11379881, 16703556, 26103963, 30337596). 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: 92867). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function. Experimental studies have shown that this missense change affects ABCA4 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 Center for Human Genetics Tuebingen RCV000078665 SCV001249465 pathogenic not provided 2022-03-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001195927 SCV001366351 likely pathogenic Age related macular degeneration 2 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PM3,PM5,PP3,PP5.
Baylor Genetics RCV000150052 SCV001521355 pathogenic Severe early-childhood-onset retinal dystrophy 2020-01-17 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000078665 SCV001905555 pathogenic not provided 2021-09-15 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000150052 SCV001976835 pathogenic Severe early-childhood-onset retinal dystrophy 2021-10-05 criteria provided, single submitter clinical testing PM1, PM2, PM5, PP3, PP5
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
Clinical Genetics, Academic Medical Center RCV000078665 SCV001920815 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000078665 SCV001958523 pathogenic not provided no assertion criteria provided clinical testing

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