Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000791743 | SCV000931004 | uncertain significance | not provided | 2025-01-29 | 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 128 of the NTHL1 protein (p.Arg128His). This variant is not present in population databases (gnomAD no frequency). 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: 639039). 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. |
| Ambry Genetics | RCV001021267 | SCV001182859 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.R128H variant (also known as c.383G>A), located in coding exon 3 of the NTHL1 gene, results from a G to A substitution at nucleotide position 383. The arginine at codon 128 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, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000791743 | SCV002549215 | uncertain significance | not provided | 2022-07-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000791743 | SCV005623916 | uncertain significance | not provided | 2024-05-30 | criteria provided, single submitter | clinical testing | The NTHL1 c.383G>A (p.Arg128His) variant has not been reported in individuals with NTHL1-related conditions in the published literature. The frequency of this variant in the general population, 0.0000066 (1/152226 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. |