Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000823171 | SCV000964020 | uncertain significance | not provided | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 150 of the NTHL1 protein (p.Ala150Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 664977). 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. |
| Ambry Genetics | RCV002332719 | SCV002635368 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-09 | criteria provided, single submitter | clinical testing | The p.A150T variant (also known as c.448G>A), located in coding exon 3 of the NTHL1 gene, results from a G to A substitution at nucleotide position 448. The alanine at codon 150 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004569779 | SCV005053727 | uncertain significance | Familial adenomatous polyposis 3 | 2024-02-27 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000823171 | SCV005623918 | uncertain significance | not provided | 2023-10-16 | criteria provided, single submitter | clinical testing | The NTHL1 c.448G>A (p.Ala150Thr) variant has not been reported individuals with NTHL1-related conditions in the published literature. The frequency of this variant in the general population, 0.00017 (3/18168 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |