ClinVar Miner

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

gnomAD frequency: 0.00015  dbSNP: rs560081099
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000627827 SCV000748707 uncertain significance Supravalvar aortic stenosis 2023-11-21 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 588 of the ELN protein (p.Val588Ile). This variant is present in population databases (rs560081099, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 524219). 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 ELN protein function with a negative predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV000762455 SCV000892777 uncertain significance not provided 2018-07-01 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
Ambry Genetics RCV002533162 SCV003552042 uncertain significance Inborn genetic diseases 2022-07-14 criteria provided, single submitter clinical testing The c.1675G>A (p.V559I) alteration is located in exon 25 (coding exon 25) of the ELN gene. This alteration results from a G to A substitution at nucleotide position 1675, causing the valine (V) at amino acid position 559 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004533301 SCV004737869 likely benign ELN-related disorder 2022-01-31 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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