ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.1675G>A (p.Val559Ile) (rs560081099)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762455 SCV000892777 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765973 SCV000897395 uncertain significance Cutis laxa, autosomal dominant 1; Williams syndrome; Supravalvar aortic stenosis 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000627827 SCV000748707 uncertain significance Supravalvar aortic stenosis 2017-11-18 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 588 of the ELN protein (p.Val588Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs560081099, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with ELN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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