Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002318083 | SCV000849753 | uncertain significance | Inborn genetic diseases | 2017-05-26 | criteria provided, single submitter | clinical testing | The p.P104A variant (also known as c.310C>G), located in coding exon 3 of the NIPBL gene, results from a C to G substitution at nucleotide position 310. The proline at codon 104 is replaced by alanine, an amino acid with highly similar properties. This variant did not co-segregate with disease in one individual tested in our laboratory. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001868356 | SCV002135775 | uncertain significance | Cornelia de Lange syndrome 1 | 2022-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 104 of the NIPBL protein (p.Pro104Ala). 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: 589143). This variant has not been reported in the literature in individuals affected with NIPBL-related conditions. This variant is present in population databases (rs772009624, gnomAD 0.03%). |