Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000146533 | SCV000193828 | uncertain significance | Cornelia de Lange syndrome 1 | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000146533 | SCV000457276 | uncertain significance | Cornelia de Lange syndrome 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Genome- |
RCV000146533 | SCV002055946 | uncertain significance | Cornelia de Lange syndrome 1 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000146533 | SCV003286849 | uncertain significance | Cornelia de Lange syndrome 1 | 2023-04-26 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NIPBL protein function. ClinVar contains an entry for this variant (Variation ID: 159044). This variant has not been reported in the literature in individuals affected with NIPBL-related conditions. This variant is present in population databases (rs201482152, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 689 of the NIPBL protein (p.Asn689Tyr). |