Submissions for variant NM_001024630.4(RUNX2):c.505C>T (p.Arg169Trp)

dbSNP: rs1203066173

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001364541	SCV001560695	pathogenic	not provided	2023-07-31	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg169 amino acid residue in RUNX2. Other variant(s) that disrupt this residue have been observed in individuals with RUNX2-related conditions (PMID: 10545612, 12424590), which suggests that this may be a clinically significant amino acid residue. 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 RUNX2 protein function. ClinVar contains an entry for this variant (Variation ID: 916703). This missense change has been observed in individuals with clinical features of cleidocranial dysplasia (PMID: 33987976; Invitae). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 169 of the RUNX2 protein (p.Arg169Trp).
CeGaT Center for Human Genetics Tuebingen	RCV001364541	SCV004163559	likely pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing	RUNX2: PM2, PM5, PP3, PS4:Supporting
Istanbul Faculty of Medicine, Istanbul University	RCV001268934	SCV001335540	likely pathogenic	Cleidocranial dysostosis	2020-05-23	no assertion criteria provided	clinical testing	Segregates in family