Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497949 | SCV000589452 | uncertain significance | not provided | 2015-07-30 | criteria provided, single submitter | clinical testing | The N59S variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The N59S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Asparagine are tolerated across species, and Serine is observed at this position in evolution. However, in silico analysis is inconsistent in its predictions as to whether or not the N59S variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV003766791 | SCV004673616 | uncertain significance | Borjeson-Forssman-Lehmann syndrome | 2023-08-28 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt PHF6 protein function. ClinVar contains an entry for this variant (Variation ID: 431889). This variant has not been reported in the literature in individuals affected with PHF6-related conditions. This variant is present in population databases (rs202007952, gnomAD 0.003%), including at least one homozygous and/or hemizygous individual. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 59 of the PHF6 protein (p.Asn59Ser). |