ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1253T>C (p.Phe418Ser) (rs794726979)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000173679 SCV000321336 pathogenic not provided 2021-01-18 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported as pathogenic in ClinVar but additional evidence is not available (ClinVar Variation ID 193580; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 28559085, 26720470, 21911583, 23499370, 30055151, 23143460, 28771251, 29555955, 28341476, 30834176)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000173679 SCV000331703 pathogenic not provided 2016-08-29 criteria provided, single submitter clinical testing
Invitae RCV000173679 SCV001205468 pathogenic not provided 2020-02-04 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 418 of the ABCA4 protein (p.Phe418Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ABCA4-related conditions (PMID: 30834176, 28341476, 29555955, 28559085, 21911583). 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: 193580). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073557 SCV001239106 pathogenic Retinal dystrophy 2019-06-15 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000173679 SCV001447928 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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