ClinVar Miner

Submissions for variant NM_024678.6(NARS2):c.1291T>C (p.Tyr431His)

gnomAD frequency: 0.00004  dbSNP: rs370150532
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001724760 SCV001950042 uncertain significance Combined oxidative phosphorylation defect type 24 2021-07-16 criteria provided, single submitter clinical testing The variant was identified in a compound heterozygous state with the variant c.167A>G, p.(Gln56Arg) in a patient with a phenotype that was compatible with a NARS2-related disorder (epileptic encephalopathy).
GeneDx RCV002267119 SCV002549470 likely pathogenic not provided 2024-11-04 criteria provided, single submitter clinical testing Reported in the single heterozygous state as a rare variant from a cohort of individuals with colorectal cancer (PMID: 26901136); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26901136)
Labcorp Genetics (formerly Invitae), Labcorp RCV002267119 SCV002953793 uncertain significance not provided 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 431 of the NARS2 protein (p.Tyr431His). This variant is present in population databases (rs370150532, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1297024). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.
PreventionGenetics, part of Exact Sciences RCV004758192 SCV005347947 uncertain significance NARS2-related disorder 2024-05-10 no assertion criteria provided clinical testing The NARS2 c.1291T>C variant is predicted to result in the amino acid substitution p.Tyr431His. This variant has been observed in an individual with an early-onset colorectal cancer (Table S3, de Voer et al. 2016. PubMed ID: 26901136). This variant is reported in 0.0094% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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