Submissions for variant NM_015559.3(SETBP1):c.2563C>A (p.Pro855Thr)

dbSNP: rs2145105580

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001774622	SCV002002941	uncertain significance	not provided	2020-02-24	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics	RCV003333177	SCV004041218	likely pathogenic	Intellectual disability, autosomal dominant 29	2023-07-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003333176	SCV004041376	likely pathogenic	Schinzel-Giedion syndrome	2023-07-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001774622	SCV004467207	uncertain significance	not provided	2023-05-20	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SETBP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1315372). 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 expected to disrupt SETBP1 protein function. 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. This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 855 of the SETBP1 protein (p.Pro855Thr).