Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000796867 | SCV000936399 | uncertain significance | not provided | 2024-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 264 of the NTHL1 protein (p.Ala264Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs2233522, gnomAD 0.003%). 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: 643211). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002422713 | SCV002677266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | The p.A264T variant (also known as c.790G>A), located in coding exon 5 of the NTHL1 gene, results from a G to A substitution at nucleotide position 790. The alanine at codon 264 is replaced by threonine, 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. |