ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.466A>G (p.Ile156Val) (rs62646863)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622993 SCV000741006 uncertain significance Inborn genetic diseases 2015-08-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626667 SCV000747369 uncertain significance Abnormal retinal morphology 2017-01-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085663 SCV000700683 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764207 SCV000895210 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
GeneDx RCV000085663 SCV000321327 uncertain significance not provided 2018-11-09 criteria provided, single submitter clinical testing The I156V variant has been reported in a patient diagnosed with Stargardt disease and was absent from 96 control alleles (Papaioannou et al., 2000). The I156V variant has also been reported as a polymorphism (Riveiro-Alvarez et al.,2009). The NHLBI Exome Sequencing Project and the 1000 Genomes Project reports that I156V was observed in 13/8600 alleles from individuals of European background, in 1/28 alleles from individuals of Spanish background and in 2/196 alleles from individuals of Italian background indicating it may be a rare benign variant in the European population. The I156V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not 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. Missense variants in nearby residues (R152Q, I153L, E161K, G172S) have been reported in the Human Gene Mutation Database in association with ABCA4-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504910 SCV000598982 likely benign Stargardt disease 1 2015-01-01 no assertion criteria provided research
Retina International RCV000085663 SCV000117803 not provided not provided no assertion provided not provided

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