ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.863G>A (p.Arg288His)

gnomAD frequency: 0.00002  dbSNP: rs148253565
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000807053 SCV000947081 uncertain significance not provided 2025-01-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 296 of the NTHL1 protein (p.Arg296His). This variant is present in population databases (rs148253565, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 651647). 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 tolerated. 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 RCV000807053 SCV001983233 uncertain significance not provided 2021-10-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002442698 SCV002682984 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-04 criteria provided, single submitter clinical testing The p.R296H variant (also known as c.887G>A), located in coding exon 6 of the NTHL1 gene, results from a G to A substitution at nucleotide position 887. The arginine at codon 296 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000807053 SCV005623939 uncertain significance not provided 2024-12-06 criteria provided, single submitter clinical testing The NTHL1 c.887G>A (p.Arg296His) variant has not been reported in individuals with NTHL1-related conditions in the published literature. The frequency of this variant in the general population, 0.000016 (4/244978 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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