ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1015T>G (p.Trp339Gly) (rs61751420)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085367 SCV000589297 likely pathogenic not provided 2018-01-04 criteria provided, single submitter clinical testing The W339G variant in the ABCA4 gene has been reported previously in multiple individuals with Stargardt disease. It has been reported along with a second variant, and also in individuals with no second variant identified (Yatsenko et al., 2001; Zernant et al., 2014). The W339G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The W339G 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret W339G as a likely pathogenic variant.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000085367 SCV000706614 uncertain significance not provided 2017-03-29 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073495 SCV001239038 pathogenic Retinal dystrophy 2019-04-05 criteria provided, single submitter clinical testing
Invitae RCV000085367 SCV001382168 pathogenic not provided 2020-09-11 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with glycine at codon 339 of the ABCA4 protein (p.Trp339Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with Stargardt disease (PMID: 11379881, 28559085). ClinVar contains an entry for this variant (Variation ID: 99025). 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.
Retina International RCV000085367 SCV000117504 not provided not provided no assertion provided not provided

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