ClinVar Miner

Submissions for variant NM_024678.6(NARS2):c.1141A>G (p.Asn381Asp)

dbSNP: rs2135213081
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV002254491 SCV002525747 uncertain significance Combined oxidative phosphorylation defect type 24 2022-06-08 criteria provided, single submitter curation This variant is interpreted as a variant of uncertain significance for Combined oxidative phosphorylation deficiency 24, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (PM5).
Illumina Laboratory Services, Illumina RCV003126207 SCV003802787 likely pathogenic not provided 2022-09-28 criteria provided, single submitter clinical testing The NARS2 c.1141A>G (p.Asn381Asp) missense variant results in the substitution of asparagine at amino acid position 381 with aspartic acid. This variant has been reported in a compound heterozygous state in one individual with combined oxidative phosphorylation deficiency (COXPD) (PMID: 35558980). Another variant at the same amino acid position, c.1142A>G (p.Asn381Ser), has been reported in a compound heterozygous state in one individual with COXPD (PMID: 25807530). The c.1141A>G variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Western blot analysis demonstrated the variant showed lower steady-state levels compared to that of the wild type (PMID: 35558980). The c.1141A>G variant lies within the catalytic domain of the protein. Based on the available evidence, the c.1141A>G (p.Asn381Asp) variant is classified as likely pathogenic for primary mitochondrial disease.

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