ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1140T>A (p.Asn380Lys) (rs61748549)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255225 SCV000321335 uncertain significance not specified 2016-07-04 criteria provided, single submitter clinical testing The N380K variant has been reported previously in the heterozygous state in individuals with Stargardt disease and autosomal recessive retinitis pigmentosa (Webster et al., 2001; Valverde et al., 2006; Valverde et al., 2007). For all reported individuals, no second ABCA4 variant was identified, and in one case the variant was identified in cis with another ABCA4 variant (Valverde et al., 2006). In addition, the N380K variant was observed in the heterozygous state in an individual with a history of autosomal recessive retinitis pigmentosa attributed to heterozygosity for two loss-of-function variants in the CEP290 gene (Eisenberger et al., 2013). Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports N380K was observed in 9/8600 alleles (0.11%) from individuals of European American background. The N380K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N380K as a variant of uncertain significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000085376 SCV000702698 uncertain significance not provided 2016-11-17 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764205 SCV000895208 uncertain significance Cone-rod dystrophy 3; Age-related macular degeneration 2; Stargardt disease 1; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000986372 SCV001135362 uncertain significance Stargardt disease 1 2019-05-28 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073759 SCV001239319 uncertain significance Retinal dystrophy 2017-11-30 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085376 SCV001247756 uncertain significance not provided 2020-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001096640 SCV001252865 uncertain significance ABCA4-Related Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV000085376 SCV001414645 uncertain significance not provided 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 380 of the ABCA4 protein (p.Asn380Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs61748549, ExAC 0.07%). This variant has been observed in individuals affected with ABCA4-related retinal dystrophy (PMID: 23755871, 26355662). ClinVar contains an entry for this variant (Variation ID: 99033). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Retina International RCV000085376 SCV000117513 not provided not provided no assertion provided not provided
Faculty of Health Sciences,Beirut Arab University RCV001257823 SCV001434607 pathogenic Autosomal recessive retinitis pigmentosa 2015-09-10 no assertion criteria provided literature only

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