Total submissions: 5
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. |
Ce |
RCV000762455 | SCV000892777 | uncertain significance | not provided | 2018-07-01 | criteria provided, single submitter | clinical testing | |
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. |
Prevention |
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). |