Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000801792 | SCV000941587 | uncertain significance | not provided | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 252 of the NTHL1 protein (p.Thr252Ser). This variant is present in population databases (rs145312239, gnomAD 0.03%). 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: 647306). 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 | RCV001026563 | SCV001188969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | The p.T252S variant (also known as c.755C>G), located in coding exon 5 of the NTHL1 gene, results from a C to G substitution at nucleotide position 755. The threonine at codon 252 is replaced by serine, an amino acid with 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. |
| Baylor Genetics | RCV004569579 | SCV005053735 | uncertain significance | Familial adenomatous polyposis 3 | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000801792 | SCV005623934 | uncertain significance | not provided | 2024-03-26 | criteria provided, single submitter | clinical testing | The NTHL1 c.755C>G (p.Thr252Ser) variant has not been reported in individuals with NTHL1-related conditions in the published literature. The frequency of this variant in the general population, 0.00031 (5/16244 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. |