Submissions for variant NM_001113491.2(SEPTIN9):c.866G>A (p.Arg289His)

gnomAD frequency: 0.00003  dbSNP: rs587781247

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003546477	SCV004275138	uncertain significance	not provided	2023-05-25	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs587781247, gnomAD 0.003%). 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 SEPT9 protein function. ClinVar contains an entry for this variant (Variation ID: 157523). This variant is also known as c.530G>A p.R177H. This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 25025039). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 271 of the SEPT9 protein (p.Arg271His).
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust	RCV000144865	SCV000172136	uncertain significance	Charcot-Marie-Tooth disease	2013-11-01	no assertion criteria provided	research