Submissions for variant NM_018122.5(DARS2):c.1375T>G (p.Cys459Gly)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003052427	SCV003345998	uncertain significance	not provided	2023-08-04	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 459 of the DARS2 protein (p.Cys459Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2131380). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DARS2 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV003138460	SCV003807549	uncertain significance	Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome	2022-06-21	criteria provided, single submitter	clinical testing	ACMG classification criteria: PM2 moderated
Genome-Nilou Lab	RCV003138460	SCV004048899	uncertain significance	Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome	2023-04-11	criteria provided, single submitter	clinical testing