Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001920212 | SCV002162564 | uncertain significance | not provided | 2023-06-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1397425). 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 SETBP1 protein function. This variant has not been reported in the literature in individuals affected with SETBP1-related conditions. This variant is present in population databases (rs370610721, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 351 of the SETBP1 protein (p.Asp351Tyr). |
| Pittsburgh Clinical Genomics Laboratory, |
RCV004784003 | SCV005397818 | uncertain significance | Schinzel-Giedion syndrome | 2024-04-26 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (G>T) at position 1051 of the coding sequence of the SETBP1 gene that results in an aspartic acid to tyrosine amino acid change at residue 351 of SET binding protein 1. This is a previously reported variant (ClinVar 1397425) that has not been observed in individuals affected by a SETBP1-related disorder in the published literature, to our knowledge. This variant is present in 8 of 1613986 alleles (0.0005%) in the gnomAD v4.0.0 population dataset. Bioinformatic tools are inconclusive if this amino acid change will be damaging or tolerated, and the Asp351 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2 |