Submissions for variant NM_024678.6(NARS2):c.500A>G (p.His167Arg)

gnomAD frequency: 0.00001  dbSNP: rs750594551

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001856178	SCV002178950	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 167 of the NARS2 protein (p.His167Arg). This variant is present in population databases (rs750594551, gnomAD 0.006%). This missense change has been observed in individual(s) with infantile-onset neurodevelopmental disorder (PMID: 28077841). ClinVar contains an entry for this variant (Variation ID: 632580). 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 NARS2 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.
Revvity Omics, Revvity	RCV001856178	SCV003813437	uncertain significance	not provided	2019-07-26	criteria provided, single submitter	clinical testing
OMIM	RCV000779620	SCV000916299	pathogenic	Combined oxidative phosphorylation defect type 24	2019-05-24	no assertion criteria provided	literature only
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,	RCV000779620	SCV001245464	uncertain significance	Combined oxidative phosphorylation defect type 24		no assertion criteria provided	clinical testing