ClinVar Miner

Submissions for variant NM_004341.5(CAD):c.5429G>A (p.Arg1810Gln)

gnomAD frequency: 0.00028  dbSNP: rs139332887
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485191 SCV000571629 likely pathogenic not provided 2023-06-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32820246, 33497533, 35242569, 28719003, 26740555, Dragolova2022[BachelorsThesis])
Mendelics RCV000986606 SCV001135642 likely pathogenic Developmental and epileptic encephalopathy, 50 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001778976 SCV002014904 likely pathogenic Infantile epileptic dyskinetic encephalopathy 2021-10-14 criteria provided, single submitter clinical testing Variant summary: CAD c.5429G>A (p.Arg1810Gln) 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 0.00034 in 235756 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in CAD causing Early Infantile Epileptic Encephalopathy, 50 (0.00034 vs 0.0011), allowing no conclusion about variant significance. c.5429G>A has been reported in the literature in individuals affected with CAD deficiency (Rymen_2020, McGraw_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000485191 SCV002147772 pathogenic not provided 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1810 of the CAD protein (p.Arg1810Gln). This variant is present in population databases (rs139332887, gnomAD 0.2%). This missense change has been observed in individual(s) with CAD-related conditions (PMID: 32820246, 33497533). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 422220). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity Omics RCV000986606 SCV004238519 likely pathogenic Developmental and epileptic encephalopathy, 50 2023-07-21 criteria provided, single submitter clinical testing

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