ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.602G>C (p.Arg201Pro) (rs367552387)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630698 SCV000751663 uncertain significance Familial dysautonomia 2017-10-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 201 of the IKBKAP protein (p.Arg201Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is present in population databases (rs367552387, ExAC 0.006%). This variant has not been reported in the literature in individuals with IKBKAP-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000630698 SCV001160349 uncertain significance Familial dysautonomia 2019-03-13 criteria provided, single submitter clinical testing The p.Arg201Pro variant (rs367552387) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.002 percent (identified on 4 out of 251,416 chromosomes) and has been reported to the ClinVar database (Variation ID: 526201). The arginine at position 201 is highly conserved and computational analyses of the effects of the p.Arg201Pro variant on protein structure and function is deleterious (SIFT: damaging, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Arg201Pro variant with certainty.

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