ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2304C>G (p.Ile768Met)

gnomAD frequency: 0.00002  dbSNP: rs946594091
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174686 SCV001337921 uncertain significance not specified 2020-01-08 criteria provided, single submitter clinical testing Variant summary: ABCA4 c.2304C>G (p.Ile768Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 31404 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2304C>G in individuals affected with Stargardt disease and no experimental evidence demonstrating an impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001873649 SCV002300599 uncertain significance not provided 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 768 of the ABCA4 protein (p.Ile768Met). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ABCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 917610). 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 not expected to disrupt ABCA4 protein function. 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.

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