Submissions for variant NM_018060.4(IARS2):c.479T>C (p.Ile160Thr)

gnomAD frequency: 0.00056  dbSNP: rs149036509

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001962442	SCV002209113	uncertain significance	not provided	2022-08-08	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 160 of the IARS2 protein (p.Ile160Thr). This variant is present in population databases (rs149036509, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with IARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1434474). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
GeneDx	RCV001962442	SCV003924606	uncertain significance	not provided	2023-05-09	criteria provided, single submitter	clinical testing	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
Mayo Clinic Laboratories, Mayo Clinic	RCV001962442	SCV005408866	uncertain significance	not provided	2023-11-13	criteria provided, single submitter	clinical testing	BS1, PP3
PreventionGenetics, part of Exact Sciences	RCV003913459	SCV004733466	likely benign	IARS2-related disorder	2023-10-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).